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CN102647999A - Composition for immunization against Staphylococcus aureus - Google Patents

Composition for immunization against Staphylococcus aureus Download PDF

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CN102647999A
CN102647999A CN2010800274105A CN201080027410A CN102647999A CN 102647999 A CN102647999 A CN 102647999A CN 2010800274105 A CN2010800274105 A CN 2010800274105A CN 201080027410 A CN201080027410 A CN 201080027410A CN 102647999 A CN102647999 A CN 102647999A
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F·巴格诺利
M·比亚吉尼
L·菲亚施
G·格兰迪
R·米什拉
N·诺拉斯
M·斯卡塞利
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Abstract

有效的金黄色葡萄球菌疫苗可能需要几种抗原性组分，因此鉴定了金黄色葡萄球菌抗原的各种组合用于免疫。这些多肽可任选与金黄色葡萄球菌糖联用。An effective S. aureus vaccine may require several antigenic components, and therefore various combinations of S. aureus antigens have been identified for use in immunization. These polypeptides may optionally be combined with S. aureus saccharides.

Description

用于免疫接种以抵御金黄色葡萄球菌的组合物Composition for immunization against Staphylococcus aureus

技术领域 technical field

本发明涉及衍生自金黄色葡萄球菌(S.aureus)的抗原和它们在免疫接种中的应用。The present invention relates to antigens derived from Staphylococcus aureus (S. aureus) and their use in immunization.

背景技术 Background technique

金黄色葡萄球菌(Staphylococcus aureus)是革兰氏阳性细菌。每年美国的死亡率超过包括HIV/AIDS在内的任何其它感染性疾病，金黄色葡萄球菌是血流、下呼吸道、皮肤和软组织感染的主要原因。目前尚无批准的疫苗。在2005年的III期临床试验中，与安慰剂组相比，基于5和8型细菌的表面多糖的混合物的疫苗(StaphVAXTM)未能降低感染。Staphylococcus aureus is a Gram-positive bacterium. Killing more people in the United States each year than any other infectious disease, including HIV/AIDS, Staphylococcus aureus is the leading cause of bloodstream, lower respiratory tract, skin and soft tissue infections. There is currently no approved vaccine. In a phase III clinical trial in 2005, a vaccine based on a mixture of surface polysaccharides of bacteria types 5 and 8 (StaphVAX ™ ) failed to reduce infection compared to placebo.

参考文献1报道了默克公司(Merck)和细胞间公司(Intercell)的“V710”疫苗正对经历心胸外科手术的患者进行2/3期试验。V710疫苗基于单抗原，IsdB[2]，这是保守性铁-螯合性细胞表面蛋白质。Reference 1 reports that Merck and Intercell's "V710" vaccine is in phase 2/3 trials in patients undergoing cardiothoracic surgery. The V710 vaccine is based on a single antigen, IsdB [2], which is a conserved iron-chelating cell surface protein.

金黄色葡萄球菌导致从皮肤感染到危及生命的疾病，例如肺炎、脑膜炎、骨髓炎、菌血症、心内膜炎、中毒性休克综合征、器官脓肿和败血症等一系列疾病。该细菌具有多种毒力因子(virulence factor)，它们在其生命周期的不同阶段差别表达，因此，能预防一种疾病的疫苗可能无法预防另一种。例如，V710疫苗可有效抵御金黄色葡萄球菌的血液扩散(hematic spread)，但对于肺炎可能无效，可能无法引发任何调理活性。本发明的目的之一是提供保护作用以免血液扩散和肺炎的疫苗，其还能引发调理应答。Staphylococcus aureus causes a range of diseases from skin infections to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, bacteremia, endocarditis, toxic shock syndrome, organ abscesses and sepsis. The bacterium has multiple virulence factors that are differentially expressed at different stages of its life cycle, so a vaccine that protects against one disease may not protect against another. For example, the V710 vaccine is effective against the hematic spread of Staphylococcus aureus, but may not be effective against pneumonia and may fail to elicit any opsonic activity. One of the objects of the present invention is to provide a vaccine that protects against hematogenous spread and pneumonia, and that also elicits an opsonized response.

因此，本领域仍需要鉴定其它和改进的抗原以便用于金黄色葡萄球菌疫苗，特别是可用于抵御多种金黄色葡萄球菌病理的疫苗。Accordingly, there remains a need in the art to identify additional and improved antigens for use in S. aureus vaccines, particularly vaccines useful against a variety of S. aureus pathologies.

发明内容 Contents of the invention

本发明鉴定了可单独或组合用于免疫接种的各种金黄色葡萄球菌多肽。这些多肽可与金黄色葡萄球菌糖或其它金黄色葡萄球菌多肽组合。该抗原可用于金黄色葡萄球菌疫苗，但也可用作免疫接种以抵御多种病原体的疫苗组分。The present invention identifies various S. aureus polypeptides that can be used alone or in combination for immunization. These polypeptides can be combined with S. aureus saccharides or other S. aureus polypeptides. This antigen can be used in S. aureus vaccines, but can also be used as a vaccine component for immunization against a variety of pathogens.

本发明人已鉴定了以下36种多肽：clfA、clfB、coA、eap、ebhA、ebpS、efb、emp、esaC、esxA、esxB、FnBA、FnBB、Hla、hlgB、hlgC、isdA、isdB、isdC、isdG、isdH、isdI、lukD、lukE、lukF、lukS、nuc、sasA、sasB、sasC、sasD、sasF、sdrC、sdrD、spa和sdrE2。该组抗原在本文称为“第一抗原组”。因此，本发明提供包含抗原组合的免疫原性组合物，所述组合包含选自下组的两种或更多种(即，2、3、4、5、6或更多种)抗原：(1)clfA抗原；(2)clfB抗原；(3)coA抗原；(4)eap抗原；(5)ebhA抗原；(6)ebpS抗原；(7)efb抗原；(8)emp抗原；(9)esaC抗原；(10)esxA抗原；(11)esxB抗原；(12)FnBA抗原；(13)FnBB抗原；(14)Hla抗原；(15)hlgB抗原；(16)hlgC抗原；(17)isdA抗原；(18)isdB抗原；(19)isdC抗原；(20)isdG抗原；(21)isdH抗原；(22)isdI抗原；(23)lukD抗原；(24)lukE抗原；(25)lukF抗原；(26)lukS抗原；(27)nuc抗原；(28)sasA抗原；(29)sasB抗原；(30)sasC抗原；(31)sasD抗原；(32)sasF抗原；(33)sdrC抗原；(34)sdrD抗原；(35)spa抗原；(36)sdrE2抗原。The inventors have identified the following 36 polypeptides: clfA, clfB, coA, eap, ebhA, ebpS, efb, emp, esaC, esxA, esxB, FnBA, FnBB, Hla, hlgB, hlgC, isdA, isdB, isdC, isdG , isdH, isdl, lukD, lukE, lukF, lukS, nuc, sasA, sasB, sasC, sasD, sasF, sdrC, sdrD, spa, and sdrE2. This group of antigens is referred to herein as the "first antigen group". Accordingly, the present invention provides immunogenic compositions comprising a combination of antigens comprising two or more (i.e., 2, 3, 4, 5, 6 or more) antigens selected from the group consisting of: ( 1) clfA antigen; (2) clfB antigen; (3) coA antigen; (4) eap antigen; (5) ebhA antigen; (6) ebpS antigen; (7) efb antigen; (8) emp antigen; (9) (10) esxA antigen; (11) esxB antigen; (12) FnBA antigen; (13) FnBB antigen; (14) Hla antigen; (15) hlgB antigen; (16) hlgC antigen; (17) isdA antigen (18) isdB antigen; (19) isdC antigen; (20) isdG antigen; (21) isdH antigen; (22) isdI antigen; (23) lukD antigen; (24) lukE antigen; (25) lukF antigen; ( 26) lukS antigen; (27) nuc antigen; (28) sasA antigen; (29) sasB antigen; (30) sasC antigen; (31) sasD antigen; (32) sasF antigen; (33) sdrC antigen; (34) sdrD antigen; (35) spa antigen; (36) sdrE2 antigen.

在该第一抗原组内，优选该36种多肽中的16种的抗原亚组，即：clfA、clfB、emp、esaC、esxA、esxB、hla、isdA、isdB、isdC、sasD、sasF、sdrC、sdrD、spa和sdrE2。因此，本发明提供包含抗原组合的免疫原性组合物，所述组合包含选自由这16种抗原构成的组的两种或更多种(即2、3、4、5、6或更多种)抗原。Within the first antigen group, antigen subgroups of 16 of the 36 polypeptides are preferred, namely: clfA, clfB, emp, esaC, esxA, esxB, hla, isdA, isdB, isdC, sasD, sasF, sdrC, sdrD, spa and sdrE2. Accordingly, the present invention provides immunogenic compositions comprising a combination of antigens comprising two or more (i.e. 2, 3, 4, 5, 6 or more) selected from the group consisting of these 16 antigens. )antigen.

本发明人鉴定到以下128种多肽：sta001、sta002、sta003、sta004、sta005、sta006、sta007、sta008、sta009、sta010、sta011、sta012、sta013、sta014、sta015、sta016、sta017、sta018、sta019、sta020、sta021、sta022、sta023、sta024、sta025、sta026、sta027、sta028、sta029、sta030、sta031、sta032、sta033、sta034、sta035、sta036、sta037、sta038、sta039、sta040、sta041、sta042、sta043、sta044、sta045、sta046、sta047、sta048、sta049、sta050、sta051、sta052、sta053、sta054、sta055、sta056、sta057、sta058、sta059、sta060、sta061、sta062、sta063、sta064、sta065、sta066、sta067、sta068、sta069、sta070、sta071、sta072、sta073、sta074、sta075、sta076、sta077、sta078、sta079、sta080、sta081、sta082、sta083、sta084、sta085、sta086、sta087、sta088、sta089、sta090、sta091、sta092、sta093、sta094、sta095、sta096、sta097、sta098、sta099、sta100、sta101、sta102、sta103、sta104、sta105、sta106、sta107、sta108、sta109、sta110、sta111、sta112、sta113、sta114、sta115、sta116、sta117、sta118、sta119、sta120、NW_6、NW_9、NW_10、NW_7、NW_8、NW_2、NW_1和NW_5。该组抗原在本文称为“第二抗原组”。因此，本发明提供包含抗原组合的免疫原性组合物，所述组合包含选自下组的两种或更多种(即2、3、4、5、6或更多种)抗原：(1)sta001抗原；(2)sta002抗原；(3)sta003抗原；(4)sta004抗原；(5)sta005抗原；(6)sta006抗原；(7)sta007抗原；(8)sta008抗原；(9)sta009抗原；(10)sta010抗原；(11)sta011抗原；(12)sta012抗原；(13)sta013抗原；(14)sta014抗原；(15)sta015抗原；(16)sta016抗原；(17)sta017抗原；(18)sta018抗原；(19)sta019抗原；(20)sta020抗原；(21)sta021抗原；(22)sta022抗原；(23)sta023抗原；(24)sta024抗原；(25)sta025抗原；(26)sta026抗原；(27)sta027抗原；(28)sta028抗原；(29)sta029抗原；(30)sta030抗原；(31)sta031抗原；(32)sta032抗原；(33)sta033抗原；(34)sta034抗原；(35)sta035抗原；(36)sta036抗原；(37)sta037抗原；(38)sta038抗原；(39)sta039抗原；(40)sta040抗原；(41)sta041抗原；(42)sta042抗原；(43)sta043抗原；(44)sta044抗原；(45)sta045抗原；(46)sta046抗原；(47)sta047抗原；(48)sta048抗原；(49)sta049抗原；(50)sta050抗原；(51)sta051抗原；(52)sta052抗原；(53)sta053抗原；(54)sta054抗原；(55)sta055抗原；(56)sta056抗原；(57)sta057抗原；(58)sta058抗原；(59)sta059抗原；(60)sta060抗原；(61)sta061抗原；(62)sta062抗原；(63)sta063抗原；(64)sta064抗原；(65)sta065抗原；(66)sta066抗原；(67)sta067抗原；(68)sta068抗原；(69)sta069抗原；(70)sta070抗原；(71)sta071抗原；(72)sta072抗原；(73)sta073抗原；(74)sta074抗原；(75)sta075抗原；(76)sta076抗原；(77)sta077抗原；(78)sta078抗原；(79)sta079抗原；(80)sta080抗原；(81)sta081抗原；(82)sta082抗原；(83)sta083抗原；(84)sta084抗原；(85)sta085抗原；(86)sta086抗原；(87)sta087抗原；(88)sta088抗原；(89)sta089抗原；(90)sta090抗原；(91)sta091抗原；(92)sta092抗原；(93)sta093抗原；(94)sta094抗原；(95)sta095抗原；(96)sta096抗原；(97)sta097抗原；(98)sta098抗原；(99)sta099抗原；(100)sta100抗原；(101)sta101抗原；(102)sta102抗原；(103)sta103抗原；(104)sta104抗原；(105)sta105抗原；(106)sta106抗原；(107)sta107抗原；(108)sta108抗原；(109)sta109抗原；(110)sta110抗原；(111)sta111抗原；(112)sta112抗原；(113)sta113抗原；(114)sta114抗原；(115)sta115抗原；(116)sta116抗原；(117)sta117抗原；(118)sta118抗原；(119)sta119抗原；(120)sta120抗原；(121)NW_6抗原；(122)NW_9抗原；(123)NW_10抗原；(124)NW_7抗原；(125)NW_8抗原；(126)NW_2抗原；(127)NW_1抗原；和(128)NW_5抗原。The inventors identified the following 128 polypeptides: sta001, sta002, sta003, sta004, sta005, sta006, sta007, sta008, sta009, sta010, sta011, sta012, sta013, sta014, sta015, sta016, sta017, sta018, sta019, sta020, sta021, sta022, sta023, sta024, sta025, sta026, sta027, sta028, sta029, sta030, sta031, sta032, sta033, sta034, sta035, sta036, sta037, sta038, sta039, sta040, sta041, sta042, sta043, sta044, sta045, sta046, sta047, sta048, sta049, sta050, sta051, sta052, sta053, sta054, sta055, sta056, sta057, sta058, sta059, sta060, sta061, sta062, sta063, sta064, sta065, sta066, sta067, sta068, sta069, sta070, sta071, sta072, sta073, sta074, sta075, sta076, sta077, sta078, sta079, sta080, sta081, sta082, sta083, sta084, sta085, sta086, sta087, sta088, sta089, sta090, sta091, sta092, sta093, sta094, sta095, sta096, sta097, sta098, sta099, sta100, sta101, sta102, sta103, sta104, sta105, sta106, sta107, sta108, sta109, sta110, sta111, sta112, sta113, sta114, sta115, sta116, sta117, sta118, sta119, sta120, NW_6, NW_9, NW_10, NW_7, NW_8, NW_2, NW_1, and NW_5. This group of antigens is referred to herein as the "second antigen group". Accordingly, the present invention provides immunogenic compositions comprising a combination of antigens comprising two or more (i.e. 2, 3, 4, 5, 6 or more) antigens selected from the group consisting of: (1 (2) sta002 antigen; (3) sta003 antigen; (4) sta004 antigen; (5) sta005 antigen; (6) sta006 antigen; (7) sta007 antigen; (8) sta008 antigen; (9) sta009 (10) sta010 antigen; (11) sta011 antigen; (12) sta012 antigen; (13) sta013 antigen; (14) sta014 antigen; (15) sta015 antigen; (16) sta016 antigen; (17) sta017 antigen; (18) sta018 antigen; (19) sta019 antigen; (20) sta020 antigen; (21) sta021 antigen; (22) sta022 antigen; (23) sta023 antigen; (24) sta024 antigen; (25) sta025 antigen; (26) (27) sta027 antigen; (28) sta028 antigen; (29) sta029 antigen; (30) sta030 antigen; (31) sta031 antigen; (32) sta032 antigen; (33) sta033 antigen; (34) sta034 (35) sta035 antigen; (36) sta036 antigen; (37) sta037 antigen; (38) sta038 antigen; (39) sta039 antigen; (40) sta040 antigen; (41) sta041 antigen; (42) sta042 antigen; (43) sta043 antigen; (44) sta044 antigen; (45) sta045 antigen; (46) sta046 antigen; (47) sta047 antigen; (48) sta048 antigen; (49) sta049 antigen; (50) sta050 antigen; (51) (52) sta052 antigen; (53) sta053 antigen; (54) sta054 antigen; (55) sta055 antigen; (56) sta056 antigen; (57) sta057 antigen; (58) sta058 antigen; (59) sta059 (60) sta060 antigen; (61) sta061 antigen; (62) sta062 antigen; (63) sta063 antigen; (64) sta064 antigen; (65) sta065 antigen; (66) sta066 antigen; (67) sta067 antigen; (68) sta068 antigen; (69) sta069 antigen; (70) sta070 antigen; (71) sta071 antigen; (72) sta072 antigen; (73) sta073 antigen; ( 74) sta074 antigen; (75) sta075 antigen; (76) sta076 antigen; (77) sta077 antigen; (78) sta078 antigen; (79) sta079 antigen; (80) sta080 antigen; (81) sta081 antigen; (82) (83) sta083 antigen; (84) sta084 antigen; (85) sta085 antigen; (86) sta086 antigen; (87) sta087 antigen; (88) sta088 antigen; (89) sta089 antigen; (90) sta090 antigen (91) sta091 antigen; (92) sta092 antigen; (93) sta093 antigen; (94) sta094 antigen; (95) sta095 antigen; (96) sta096 antigen; (97) sta097 antigen; (98) sta098 antigen; ( (100) sta100 antigen; (101) sta101 antigen; (102) sta102 antigen; (103) sta103 antigen; (104) sta104 antigen; (105) sta105 antigen; (106) sta106 antigen; (107) (108) sta108 antigen; (109) sta109 antigen; (110) sta110 antigen; (111) sta111 antigen; (112) sta112 antigen; (113) sta113 antigen; (114) sta114 antigen; (115) sta115 antigen (116) sta116 antigen; (117) sta117 antigen; (118) sta118 antigen; (119) sta119 antigen; (120) sta120 antigen; (121) NW_6 antigen; (122) NW_9 antigen; (123) NW_10 antigen; ( 124) NW_7 antigen; (125) NW_8 antigen; (126) NW_2 antigen; (127) NW_1 antigen; and (128) NW_5 antigen.

在128种抗原的第二抗原组内，113种抗原的优选亚组从该清单中省去(81)和(107)到(120)。Within the second antigen group of 128 antigens, a preferred subgroup of 113 antigens was omitted from this list (81) and (107) to (120).

在第二抗原组内，本文将128种多肽的27种亚组称为“第三抗原组”，即：sta001、sta002、sta003、sta004、sta005、sta006、sta007、sta008、sta009、sta010、sta019、sta028、sta040、sta049、sta057、sta064、sta073、sta095、sta098、sta101、sta105、NW_1、NW_6、NW_7、NW_8、NW_9和NW_10。因此，本发明提供包含抗原组合的免疫原性组合物，所述组合包含选自所述第三抗原组的两种或更多种(即2、3、4、5、6或更多种)抗原：Within the second antigen group, 27 subgroups of 128 polypeptides are referred to herein as the "third antigen group", namely: sta001, sta002, sta003, sta004, sta005, sta006, sta007, sta008, sta009, sta010, sta019, sta028, sta040, sta049, sta057, sta064, sta073, sta095, sta098, sta101, sta105, NW_1, NW_6, NW_7, NW_8, NW_9, and NW_10. Accordingly, the invention provides an immunogenic composition comprising a combination of antigens comprising two or more (i.e. 2, 3, 4, 5, 6 or more) selected from said third group of antigens. antigen:

本文将在第二抗原组中但不在第三抗原组中的101种抗原称为“第四抗原组”。在101种抗原的第四抗原组中，86种抗原的优选亚组从以上清单中省去(81)和(107)到(120)。因此，第二抗原组由第三和第四抗原组的组合构成。The 101 antigens that are in the second antigen group but not in the third antigen group are referred to herein as the "fourth antigen group". In the fourth antigen group of 101 antigens, a preferred subgroup of 86 antigens was omitted from the list above (81) and (107) to (120). Thus, the second antigenic group consists of a combination of the third and fourth antigenic groups.

在第二抗原组内，本文将128种多肽的8种亚组称为“第五抗原组”，即：sta004、sta006、sta007、sta011、sta028、sta060、sta098和sta112。本发明提供包含抗原组合的免疫原性组合物，所述组合包含选自第五抗原组的两种或更多种(即2、3、4、5、6或更多种)抗原：Within the second antigen group, eight subgroups of 128 polypeptides are referred to herein as the "fifth antigen group", namely: sta004, sta006, sta007, sta011, sta028, sta060, sta098, and sta112. The present invention provides immunogenic compositions comprising a combination of antigens comprising two or more (i.e. 2, 3, 4, 5, 6 or more) antigens selected from a fifth group of antigens:

在第一抗原组的36种抗原内，有630种可能的不同抗原配对。本文公开了所有此类配对，它们是本发明的一部分。因此，本发明提供包含抗原配对的免疫原性组合物，其中所述配对是所述630种配对之一。Within the 36 antigens of the first antigen group, there are 630 possible different antigen pairings. All such pairings are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising an antigen pair, wherein said pair is one of said 630 pairs.

在第二抗原组的128种抗原内，有8128种可能的不同抗原配对。本文公开了所有此类配对，它们是本发明的一部分。因此，本发明提供包含抗原配对的免疫原性组合物，其中所述配对是所述8128种配对之一。Within the 128 antigens of the second antigen group, there are 8128 possible different antigen pairings. All such pairings are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising an antigen pair, wherein said pair is one of said 8128 pairs.

在第二抗原组的优选113种抗原内，有6328种可能的不同抗原配对。本文公开了所有此类配对，它们是本发明的一部分。因此，本发明提供包含抗原配对的免疫原性组合物，其中所述配对是所述6328种配对之一。Within the preferred 113 antigens of the second antigen group, there are 6328 possible different antigen pairs. All such pairings are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising an antigen pair, wherein said pair is one of said 6328 pairs.

在第三抗原组的优选27种抗原内，有351种可能的不同抗原配对。本文公开了所有此类配对，它们是本发明的一部分。因此，本发明提供包含抗原配对的免疫原性组合物，其中所述配对是所述351种配对之一。Within the preferred 27 antigens of the third antigen group, there are 351 possible different antigen pairs. All such pairings are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising an antigen pair, wherein said pair is one of said 351 pairs.

在第四抗原组的优选101种抗原内，有5050种可能的不同抗原配对。本文公开了所有此类配对，它们是本发明的一部分。因此，本发明提供包含抗原配对的免疫原性组合物，其中所述配对是所述5050种配对之一。Within the preferred 101 antigens of the fourth antigen group, there are 5050 possible different antigen pairs. All such pairings are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising an antigen pair, wherein said pair is one of said 5050 pairs.

在第四抗原组的优选86种抗原内，有3655种可能的不同抗原配对。本文公开了所有此类配对，它们是本发明的一部分。因此，本发明提供包含抗原配对的免疫原性组合物，其中所述配对是所述3655种配对之一。Within the preferred 86 antigens of the fourth antigen group, there are 3655 possible different antigen pairs. All such pairings are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising an antigen pair, wherein said pair is one of said 3655 pairs.

在一个实施方式中，组合物包含选自第一抗原组的至少一种抗原(即，1、2、3、4、5、6或更多种)和选自第二抗原组的至少一种抗原(即，1、2、3、4、5、6或更多种)。第一抗原组的抗原可选自16种抗原的优选亚组，第二抗原组的抗原可选自第三抗原组或第五抗原组。In one embodiment, the composition comprises at least one antigen (i.e., 1, 2, 3, 4, 5, 6 or more) selected from a first group of antigens and at least one antigen selected from a second group of antigens. Antigens (ie, 1, 2, 3, 4, 5, 6 or more). The antigens of the first antigen group can be selected from a preferred subgroup of 16 antigens, and the antigens of the second antigen group can be selected from the third antigen group or the fifth antigen group.

本发明还提供包含抗原组合的免疫原性组合物，所述组合包含选自下组的两种或更多种(即2、3、4、5、6或更多种)抗原：(1)clfA抗原；(2)clfB抗原；(3)sdrE2抗原；(4)sdrC抗原；(5)SasF抗原；(6)emp抗原；(7)sdrD抗原；(8)spa抗原；(9)esaC抗原；(10)esxA抗原；(11)esxB抗原；(12)sta006抗原；(13)isdC抗原；(14)hla抗原；(15)sta011抗原；(16)isdA抗原；(17)isdB抗原；(18)sasF抗原。有时本文将18种抗原的该组称为“第六抗原组”。The present invention also provides immunogenic compositions comprising a combination of antigens comprising two or more (i.e. 2, 3, 4, 5, 6 or more) antigens selected from the group consisting of: (1) clfA antigen; (2) clfB antigen; (3) sdrE2 antigen; (4) sdrC antigen; (5) SasF antigen; (6) emp antigen; (7) sdrD antigen; (8) spa antigen; (9) esaC antigen (10) esxA antigen; (11) esxB antigen; (12) sta006 antigen; (13) isdC antigen; (14) hla antigen; (15) sta011 antigen; (16) isdA antigen; (17) isdB antigen; ( 18) sasF antigen. This group of 18 antigens is sometimes referred to herein as the "sixth antigen group".

本发明还提供包含抗原组合的免疫原性组合物，所述组合包含选自下组的两种或更多种(即，2、3、4或5种)抗原：(1)esxA抗原；(2)esxB抗原；(3)sta006抗原；(4)hla抗原；和/或(5)sta011抗原。该组合物还可包含佐剂，例如氢氧化铝佐剂。The present invention also provides an immunogenic composition comprising a combination of antigens comprising two or more (i.e., 2, 3, 4 or 5) antigens selected from the group consisting of: (1) esxA antigen; ( 2) esxB antigen; (3) sta006 antigen; (4) hla antigen; and/or (5) sta011 antigen. The composition may also contain an adjuvant, such as aluminum hydroxide adjuvant.

本发明的优选组合是其中两种或更多种抗原协同作用的组合。因此，通过联合给药获得的抵御金黄色葡萄球菌疾病的保护作用超过它们各自保护效力的简单加和所预期的效果。A preferred combination of the present invention is one in which two or more antigens act synergistically. Thus, the protection against S. aureus disease obtained by the combined administration exceeds what would be expected from the simple summation of their individual protective potencies.

感兴趣的具体组合包括但不限于：Specific combinations of interest include, but are not limited to:

(1)包含以下抗原的免疫原性组合物：sdrD抗原、sdrE2抗原和isdC抗原。sdrD和sdrE2抗原可有用地组合成下述杂合多肽，例如，SdrDE杂合体，其中sdrE2抗原在sdrD抗原的下游。(1) An immunogenic composition comprising the following antigens: sdrD antigen, sdrE2 antigen and isdC antigen. The sdrD and sdrE2 antigens can be usefully combined into hybrid polypeptides, eg, SdrDE hybrids, wherein the sdrE2 antigen is downstream of the sdrD antigen.

(2)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原和sdrC抗原。(2) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen and sdrC antigen.

(3)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原、sdrC抗原和clfA抗原。(3) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen, sdrC antigen and clfA antigen.

(4)包含以下抗原的免疫原性组合物：sdrD抗原、a sdrE2抗原、isdC抗原和sta011抗原。sdrD和sdrE2抗原可有用地组合成下述杂合多肽，例如，SdrDE杂合体，其中sdrE2抗原在sdrD抗原的下游。(4) An immunogenic composition comprising the following antigens: sdrD antigen, a sdrE2 antigen, isdC antigen and sta011 antigen. The sdrD and sdrE2 antigens can be usefully combined into hybrid polypeptides, eg, SdrDE hybrids, wherein the sdrE2 antigen is downstream of the sdrD antigen.

(5)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原、sdrC抗原和sta006抗原。(5) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen, sdrC antigen and sta006 antigen.

(6)包含以下抗原的免疫原性组合物：sdrD抗原、sdrE2抗原、isdC抗原和hla抗原。SdrD和sdrE2抗原可有用地组合成下述杂合多肽，例如，SdrDE杂合体，其中sdrE2抗原在sdrD抗原的下游。Hla抗原可以是脱毒突变体，例如包含H35L突变。(6) An immunogenic composition comprising the following antigens: sdrD antigen, sdrE2 antigen, isdC antigen and hla antigen. The SdrD and sdrE2 antigens can be usefully combined into hybrid polypeptides, eg, SdrDE hybrids, wherein the sdrE2 antigen is downstream of the sdrD antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(7)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原、sdrC抗原和esxA抗原。(7) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen, sdrC antigen and esxA antigen.

(8)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原和hla抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。Hla抗原可以是脱毒突变体，例如包含H35L突变。(8) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen and hla antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(9)包含以下抗原的免疫原性组合物：sdrD抗原、sdrE2抗原、isdC抗原和esxA抗原。SdrD和sdrE2抗原可有用地组合成下述杂合多肽，例如，SdrDE杂合体，其中sdrE2抗原在sdrD抗原的下游。(9) An immunogenic composition comprising the following antigens: sdrD antigen, sdrE2 antigen, isdC antigen and esxA antigen. The SdrD and sdrE2 antigens can be usefully combined into hybrid polypeptides, eg, SdrDE hybrids, wherein the sdrE2 antigen is downstream of the sdrD antigen.

(10)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原和sta011抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体。(10) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen and sta011 antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids.

(11)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原和sta011抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。(11) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen and sta011 antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen.

(12)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原、sdrC抗原和spa抗原。(12) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen, sdrC antigen and spa antigen.

(13)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、isdA抗原、sta006抗原、sta011抗原和spa抗原。esxA和esxB抗原可组合成下述杂合多肽，例如，EsxAB杂合体。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。spa抗原可以是全长spa抗原的片段，例如经突变破坏或降低其与IgG Fc结合的Spa(D)结构域。(13) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, isdA antigen, sta006 antigen, sta011 antigen and spa antigen. The esxA and esxB antigens can be combined into hybrid polypeptides, eg, EsxAB hybrids. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157. The spa antigen may be a fragment of the full-length spa antigen, such as the Spa(D) domain mutated to disrupt or reduce its binding to IgG Fc.

(14)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、Hla抗原、sta006抗原和sta011抗原。esxA和esxB抗原可组合成下述杂合多肽，例如，EsxAB杂合体。Hla抗原可以是脱毒突变体，例如包含H35L突变。(14) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, Hla antigen, sta006 antigen and sta011 antigen. The esxA and esxB antigens can be combined into hybrid polypeptides, eg, EsxAB hybrids. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(15)包含以下抗原的免疫原性组合物：sdrD抗原、sdrE2抗原、isdC抗原和sdrE2抗原。SdrD和sdrE2抗原可有用地组合成下述杂合多肽，例如，SdrDE杂合体，其中sdrE2抗原在sdrD抗原的下游。(15) An immunogenic composition comprising the following antigens: sdrD antigen, sdrE2 antigen, isdC antigen and sdrE2 antigen. The SdrD and sdrE2 antigens can be usefully combined into hybrid polypeptides, eg, SdrDE hybrids, wherein the sdrE2 antigen is downstream of the sdrD antigen.

(16)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原和hla抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。Hla抗原可以是脱毒突变体，例如包含H35L突变。(16) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen and hla antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(17)包含以下抗原的免疫原性组合物：hla抗原、isdA抗原、sta006抗原和sta011抗原。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。Hla抗原可以是脱毒突变体，例如包含H35L突变。(17) An immunogenic composition comprising the following antigens: hla antigen, isdA antigen, sta006 antigen and sta011 antigen. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(18)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原和isdA抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。(18) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen and isdA antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157.

(19)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原、sdrC抗原和hla抗原。Hla抗原可以是脱毒突变体，例如包含H35L突变。(19) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen, sdrC antigen and hla antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(20)包含以下抗原的免疫原性组合物：Hla抗原、sta006抗原和sta011抗原。Hla抗原可以是脱毒突变体，例如包含H35L突变。(20) An immunogenic composition comprising the following antigens: Hla antigen, sta006 antigen and sta011 antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(21)包含以下抗原的免疫原性组合物：esxA抗原和esxB抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。(21) An immunogenic composition comprising the following antigens: esxA antigen and esxB antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen.

(22)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原和sta006抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。(22) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen and sta006 antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen.

(23)包含以下抗原的免疫原性组合物：spa抗原、sta006抗原和sta011抗原。spa抗原可以是全长spa抗原的片段，例如经突变破坏或降低其与IgGFc结合的Spa(D)结构域。(23) An immunogenic composition comprising the following antigens: spa antigen, sta006 antigen and sta011 antigen. The spa antigen may be a fragment of the full-length spa antigen, eg, the Spa(D) domain mutated to disrupt or reduce its binding to IgG Fc.

(24)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、isdA抗原、sta006抗原和sta011抗原。esxA和esxB抗原可组合成下述杂合多肽，例如，EsxAB杂合体。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。(24) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, isdA antigen, sta006 antigen and sta011 antigen. The esxA and esxB antigens can be combined into hybrid polypeptides, eg, EsxAB hybrids. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157.

(25)包含以下抗原的免疫原性组合物：sta006抗原和sta011抗原。(25) An immunogenic composition comprising the following antigens: sta006 antigen and sta011 antigen.

(26)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原、isdA抗原和clfB抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。clfB抗原可以是全长clfBA抗原的片段，例如SEQ ID NO：163。(26) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen, isdA antigen and clfB antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157. The clfB antigen can be a fragment of the full length clfBA antigen, for example SEQ ID NO: 163.

(27)包含以下抗原的免疫原性组合物：sta006抗原、sta011抗原和sta019抗原。(27) An immunogenic composition comprising the following antigens: sta006 antigen, sta011 antigen and sta019 antigen.

(28)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原、hla抗原和clfB抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。clfB抗原可以是全长clfBA抗原的片段，例如SEQ ID NO：163。Hla抗原可以是脱毒突变体，例如包含H35L突变。(28) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen, hla antigen and clfB antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The clfB antigen can be a fragment of the full length clfBA antigen, for example SEQ ID NO: 163. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(29)包含以下抗原的免疫原性组合物：sta006抗原、sta011抗原、sta019抗原和hla抗原。Hla抗原可以是脱毒突变体，例如包含H35L突变。(29) An immunogenic composition comprising the following antigens: sta006 antigen, sta011 antigen, sta019 antigen and hla antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation.

(30)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原、sta011抗原和clfB抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。clfB抗原可以是全长clfBA抗原的片段，例如SEQ ID NO：163。(30) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen, sta011 antigen and clfB antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The clfB antigen can be a fragment of the full length clfBA antigen, for example SEQ ID NO: 163.

(31)包含以下抗原的免疫原性组合物：spa抗原、esxA抗原、esxB抗原、sta006抗原和sta011抗原。spa抗原可以是全长spa抗原的片段，例如经突变破坏或降低其与IgG Fc结合的Spa(D)结构域。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体。(31) An immunogenic composition comprising the following antigens: spa antigen, esxA antigen, esxB antigen, sta006 antigen and sta011 antigen. The spa antigen may be a fragment of the full-length spa antigen, such as the Spa(D) domain mutated to disrupt or reduce its binding to IgG Fc. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids.

(32)包含以下抗原的免疫原性组合物：sdrD抗原、sdrE2抗原、isdC抗原和esxB抗原。SdrD和sdrE2抗原可用于组合成下述杂合多肽，例如，SdrDE杂合体，其中sdrE2抗原在sdrD抗原的下游。(32) An immunogenic composition comprising the following antigens: sdrD antigen, sdrE2 antigen, isdC antigen and esxB antigen. The SdrD and sdrE2 antigens can be used in combination to form hybrid polypeptides, eg, SdrDE hybrids, wherein the sdrE2 antigen is downstream of the sdrD antigen.

(33)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原、sta011抗原和sta019抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。(33) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen, sta011 antigen and sta019 antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen.

(34)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原、sta006抗原、isdA抗原和sdrD抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。sdrD抗原可以是全长sdrD抗原的片段，例如SEQ ID NO：156。(34) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen, sta006 antigen, isdA antigen and sdrD antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157. The sdrD antigen may be a fragment of the full-length sdrD antigen, such as SEQ ID NO: 156.

(35)包含以下抗原的免疫原性组合物：esxA抗原、esxB抗原和isdA抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。isdA抗原可以是全长isdA抗原的片段，例如SEQ ID NO：157。(35) An immunogenic composition comprising the following antigens: esxA antigen, esxB antigen and isdA antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen. The isdA antigen can be a fragment of the full length isdA antigen, for example SEQ ID NO: 157.

(36)包含以下抗原的免疫原性组合物：sasD抗原、clfB抗原、sdrC抗原、esxA抗原和esxB抗原。esxA和esxB抗原可有用地组合成下述杂合多肽，例如，EsxAB杂合体，其中esxB抗原在esxA抗原的下游。(36) An immunogenic composition comprising the following antigens: sasD antigen, clfB antigen, sdrC antigen, esxA antigen and esxB antigen. The esxA and esxB antigens can be usefully combined into hybrid polypeptides, eg, EsxAB hybrids, in which the esxB antigen is downstream of the esxA antigen.

(37)包含以下抗原的免疫原性组合物：Hla抗原、spa抗原、sta006抗原和sta011抗原。Hla抗原可以是脱毒突变体，例如包含H35L突变。spa抗原可以是全长spa抗原的片段，例如经突变破坏或降低其与IgG Fc结合的Spa(D)结构域。(37) An immunogenic composition comprising the following antigens: Hla antigen, spa antigen, sta006 antigen and sta011 antigen. The Hla antigen may be a detoxified mutant, for example comprising the H35L mutation. The spa antigen may be a fragment of the full-length spa antigen, such as the Spa(D) domain mutated to disrupt or reduce its binding to IgG Fc.

在一些实施方式中，这些37种组合物中的任一种可包含附加的葡萄球菌抗原，这些其它抗原可以是多肽和/或糖。例如，它们还可有用地包含一种或多种金黄色葡萄球菌荚膜糖偶联物，例如针对血清型5和/或血清型8菌株。包含一种或两种此类偶联物对于组合(8)、(10)、(20)、(23)、(25)、(31)和(37)尤其有用。In some embodiments, any of these 37 compositions can include additional staphylococcal antigens, and these other antigens can be polypeptides and/or carbohydrates. For example, they may also usefully comprise one or more S. aureus capsular glycoconjugates, eg for serotype 5 and/or serotype 8 strains. Inclusion of one or two such conjugates is especially useful for combinations (8), (10), (20), (23), (25), (31 ) and (37).

在其它实施方式中，这些37种组合物不含附加的葡萄球菌多肽抗原。在其它实施方式中，这些37种组合物不含附加抗原。In other embodiments, these 37 compositions do not contain additional staphylococcal polypeptide antigens. In other embodiments, these 37 compositions do not contain additional antigens.

本发明还提供包含以下氨基酸序列的多肽：(a)与SEQ ID NO：151有80％或更高相同性(例如，80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)的氨基酸序列；和/或(b)包含SEQ IDNO：151的氨基酸1-97的至少‘n’个毗连氨基酸和SEQ ID NO：151的氨基酸104-207的至少‘n’个毗连氨基酸的片段的氨基酸序列，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。本发明还提供包含以下氨基酸序列的多肽：(a)与SEQ ID NO：152有80％或更高相同性(例如，80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)的氨基酸序列；和/或(b)包含SEQ ID NO：152的氨基酸1-104的至少‘n’个毗连氨基酸和SEQ ID NO：152的氨基酸111-207的至少‘n’个毗连氨基酸的片段的氨基酸序列，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些多肽可引发(例如，给予人时)同时识别包含SEQ ID NO：10的野生型葡萄球菌蛋白和包含SEQ ID NO：11的野生型葡萄球菌蛋白的抗体。因此，该免疫应答同时识别抗原esxA和esxB。(b)的优选片段提供SEQID NO：10的表位和SEQ ID NO：11的表位。本发明还提供包含此类蛋白质和佐剂，例如氢氧化铝佐剂的组合的免疫原性组合物。The present invention also provides polypeptides comprising the following amino acid sequences: (a) having 80% or more identity to SEQ ID NO: 151 (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94% %, 95%, 96%, 97%, 98%, 99%, 99.5% or higher); and/or (b) at least 'n' contiguous sequences comprising amino acids 1-97 of SEQ ID NO: 151 Amino acids and amino acid sequences of fragments of at least 'n' contiguous amino acids of amino acids 104-207 of SEQ ID NO: 151, wherein 'n' is 7 or higher (e.g. 8, 10, 12, 14, 16, 18, 20 , 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). The present invention also provides polypeptides comprising the following amino acid sequences: (a) having 80% or more identity to SEQ ID NO: 152 (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94% %, 95%, 96%, 97%, 98%, 99%, 99.5% or higher) amino acid sequence; and/or (b) comprising at least 'n' of amino acids 1-104 of SEQ ID NO:152 Amino acid sequence of contiguous amino acids and fragments of at least 'n' contiguous amino acids of amino acids 111-207 of SEQ ID NO: 152, wherein 'n' is 7 or higher (e.g. 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These polypeptides can elicit (e.g., when administered to a human) antibodies that recognize both a wild-type staphylococcal protein comprising SEQ ID NO: 10 and a wild-type staphylococcal protein comprising SEQ ID NO: 11. Thus, the immune response recognizes both antigens esxA and esxB. Preferred fragments of (b) provide the epitope of SEQ ID NO: 10 and the epitope of SEQ ID NO: 11. The invention also provides immunogenic compositions comprising such proteins in combination with an adjuvant, eg aluminum hydroxide adjuvant.

本发明还提供包含以下氨基酸序列的多肽：(a)与SEQ ID NO：241有80％或更高相同性(例如，80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)的氨基酸序列；和/或(b)同时包含SEQ ID NO：241的氨基酸1-96的至少‘n’个毗连氨基酸的片段和SEQ IDNO：241的氨基酸103-205的至少‘n’个毗连氨基酸的片段的氨基酸序列，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些多肽可引发(例如，给予人时)同时识别包含SEQ ID NO：10的野生型葡萄球菌蛋白和包含SEQ ID NO：11的野生型葡萄球菌蛋白的抗体。因此，该免疫应答同时识别抗原esxA和esxB。(b)的优选片段提供SEQ ID NO：10的表位和SEQ IDNO：11的表位。本发明还提供包含此类蛋白质和佐剂，例如氢氧化铝佐剂的组合的免疫原性组合物。The present invention also provides polypeptides comprising the following amino acid sequences: (a) having 80% or more identity to SEQ ID NO: 241 (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94% %, 95%, 96%, 97%, 98%, 99%, 99.5% or higher) amino acid sequence; and/or (b) simultaneously comprising at least 'n' of amino acids 1-96 of SEQ ID NO:241 Amino acid sequences of fragments of contiguous amino acids and fragments of at least 'n' contiguous amino acids of amino acids 103-205 of SEQ ID NO: 241, wherein 'n' is 7 or higher (e.g., 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These polypeptides can elicit (e.g., when administered to a human) antibodies that recognize both a wild-type staphylococcal protein comprising SEQ ID NO: 10 and a wild-type staphylococcal protein comprising SEQ ID NO: 11. Thus, the immune response recognizes both antigens esxA and esxB. Preferred fragments of (b) provide the epitope of SEQ ID NO: 10 and the epitope of SEQ ID NO: 11. The invention also provides immunogenic compositions comprising such proteins in combination with an adjuvant, eg aluminum hydroxide adjuvant.

本发明还提供包含葡萄球菌溶血素序列的多肽，其中该序列不含与SEQ ID NO：217有至少90％相同性的序列，但能引发杀伤葡萄球菌的抗体。该多肽可具有与SEQ ID NO：218具有至少80％或更高相同性(例如，80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)的第一序列和与SEQ ID NO：219具有至少80％或更高相同性(例如，80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)的第二序列，其中该第一和第二序列直接相连或通过具有少于40个氨基酸(例如，≤35个氨基酸、≤30个氨基酸、≤25个氨基酸、≤20个氨基酸、≤15个氨基酸、≤10个氨基酸、≤5个氨基酸)的间插氨基酸序列相连。SEQ ID NO：189和216是此类多肽的例子，其中该第一和第二序列通过四肽PSGS序列(SEQ ID NO：225)相连。The present invention also provides a polypeptide comprising a staphylolysin sequence, wherein the sequence does not contain a sequence at least 90% identical to SEQ ID NO: 217, but is capable of eliciting antibodies that kill Staphylococcus. The polypeptide may have at least 80% or more identity to SEQ ID NO: 218 (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% %, 98%, 99%, 99.5% or higher) and have at least 80% or higher identity (e.g., 80%, 85%, 90%, 91%, 92% identity to SEQ ID NO: 219) %, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or higher) of the second sequence, wherein the first and second sequences are directly linked or by having less than 40 amino acids (eg, ≤35 amino acids, ≤30 amino acids, ≤25 amino acids, ≤20 amino acids, ≤15 amino acids, ≤10 amino acids, ≤5 amino acids) with intervening amino acid sequences connected. SEQ ID NO: 189 and 216 are examples of such polypeptides, wherein the first and second sequences are linked by the tetrapeptide PSGS sequence (SEQ ID NO: 225).

本发明还提供包含Sta011抗原和Ca++离子的免疫原性组合物。该抗原和Ca++离子可形成配合物，例如抗原中的原子可与Ca++离子形成配位键。该免疫原性组合物还可包含佐剂。The present invention also provides immunogenic compositions comprising the Sta011 antigen and Ca ++ ions. The antigen and Ca ++ ions can form complexes, for example atoms in the antigen can form coordination bonds with Ca ++ ions. The immunogenic composition may also contain an adjuvant.

本发明还提供Sta011抗原的寡聚物，还提供包含此类寡聚物的免疫原性组合物。该寡聚物可以是二聚体、三聚体、四聚体、五聚体、六聚体、七聚体、八聚体或更高的聚体。寡聚物可包含Ca++离子，包含Sta011寡聚物的组合物可包含5-500mM Ca++离子。The invention also provides oligomers of the Sta011 antigen, as well as immunogenic compositions comprising such oligomers. The oligomers may be dimers, trimers, tetramers, pentamers, hexamers, heptamers, octamers or higher. The oligomers may comprise Ca ++ ions and compositions comprising Sta011 oligomers may comprise 5-500 mM Ca ++ ions.

其它多肽抗原Other peptide antigens

除了本发明各种抗原组的抗原外，免疫原性组合物可包含一种或多种以下的金黄色葡萄球菌抗原(或包含其免疫原性片段的抗原)以增强该组合物引发的免疫应答抵御金黄色葡萄球菌的效力[例如，参见参考文献3-10]：In addition to the antigens of the various antigenic groups of the invention, the immunogenic composition may contain one or more of the following S. aureus antigens (or antigens comprising immunogenic fragments thereof) to enhance the immune response elicited by the composition Efficacy against Staphylococcus aureus [eg see refs 3-10]:

●AhpC● AhpC

●AhpF●AhpF

●自溶素酰胺酶●Autolysin amidase

●自溶素葡萄糖胺酶●Autolysin glucosaminidase

●胶原结合蛋白CAN●Collagen-binding protein CAN

●EbhB●EbhB

●GehD脂肪酶●GehD lipase

●肝素结合蛋白HBP(17kDa)●Heparin-binding protein HBP (17kDa)

●层粘连蛋白受体●Laminin receptor

●MAP●MAP

●MntC(也称为SitC)●MntC (also known as SitC)

●MRPII●MRPII

●Npase●Npase

●ORF0594●ORF0594

●ORF0657n●ORF0657n

●ORF0826●ORF0826

●PBP4●PBP4

●RAP(RNA III活化蛋白)●RAP (RNA III activating protein)

●Sai-1●Sai-1

●SasK●SasK

●SBI●SBI

●SdrG●SdrG

●SdrH●SdrH

●SSP-1●SSP-1

●SSP-2●SSP-2

●玻连蛋白-结合蛋白Vitronectin-binding protein

与糖组合combined with sugar

本发明抗原组中鉴定的各抗原可与偶联糖抗原联用。因此，本发明提供包含以下组合的免疫原性组合物：Each of the antigens identified in the panel of antigens of the present invention can be used in combination with conjugated carbohydrate antigens. Accordingly, the present invention provides immunogenic compositions comprising the combination of:

(1)选自第一、第二、第三或第四抗原组(如上所述)的一种或多种抗原；和(1) one or more antigens selected from the first, second, third or fourth antigen group (as described above); and

(2)一种或多种金黄色葡萄球菌表多糖和载体蛋白的偶联物。(2) One or more conjugates of Staphylococcus aureus exopolysaccharide and carrier protein.

该组合的组分(2)中所用的偶联物包括糖部分和载体部分。糖部分来自金黄色葡萄球菌表多糖，其是多聚-N-乙酰氨基葡萄糖(PNAG)。该糖可以是多糖，其尺寸在细菌表多糖纯化期间产生，或是通过片段化此类多糖获得的寡糖，例如尺寸在超过400kDa到75和400kDa之间，或在10和75kDa之间，或最多30个重复单元。糖部分可具有不同的N-乙酰化程度，如参考文献11所述，PNAG可以是低于40％N-乙酰化(例如，低于35、30、20、15、10或5％N-乙酰化；脱乙酰化PNAG也称为dPNAG)。PNAG的脱乙酰化表位可引发能介导调理杀伤的抗体。PNAG可以O-琥珀酰化或未O-琥珀酰化，例如其可在低于25、20、15、10、5、2、1或0.1％的残基上O-琥珀酰化。The conjugate used in component (2) of the combination includes a sugar moiety and a carrier moiety. The sugar moiety is derived from the S. aureus exopolysaccharide, which is poly-N-acetylglucosamine (PNAG). The sugar may be a polysaccharide of a size produced during the purification of bacterial epipolysaccharides, or an oligosaccharide obtained by fragmenting such polysaccharides, for example between 75 and 400 kDa in size, or between 10 and 75 kDa, or Up to 30 repeating units. Sugar moieties can have varying degrees of N-acetylation, and as described in reference 11, PNAG can be less than 40% N-acetylated (e.g., less than 35, 30, 20, 15, 10, or 5% N-acetylated deacetylated PNAG (also known as dPNAG). The deacetylated epitope of PNAG elicits antibodies that mediate opsonic killing. PNAG may or may not be O-succinylated, for example it may be O-succinylated on less than 25, 20, 15, 10, 5, 2, 1 or 0.1 % of the residues.

本发明还提供一种包含以下组合的免疫原性组合物：The present invention also provides an immunogenic composition comprising:

(1)选自第一、第二、第三或第四抗原组的一种或多种抗原；和(1) one or more antigens selected from the first, second, third or fourth antigen group; and

(2)金黄色葡萄球菌荚膜糖和载体蛋白的一种或多种偶联物。(2) One or more conjugates of Staphylococcus aureus capsular saccharide and carrier protein.

该组合的组分(2)中所用的偶联物包括糖部分和载体部分。所述糖部分来自金黄色葡萄球菌的荚膜糖。所述糖可以是多糖，其尺寸在细菌荚膜糖的纯化期间产生，或者可以是片段化此类多糖获得的寡糖。可以从金黄色葡萄球菌的任何合适菌株(或具有相似或相同糖的任何细菌)获得荚膜糖，例如来自5型和/或8型金黄色葡萄球菌菌株和/或336型金黄色葡萄球菌菌株。感染性金黄色葡萄球菌的大多数菌株含有5型或8型荚膜糖。二者在其重复单元中均具有FucNAcp以及ManNAcA，其可用于引入巯基以供连接。5型糖的重复单元是→4)-β-D-ManNAcA-(1→4)-α-L-FucNAc(3OAc)-(1→3)-β-D-FucNAc-(1→，而8型糖的重复单元是→3)-β-D-ManNAcA(4OAc)-(1→3)-α-L-FucNAc(1→3)-α-D-FucNAc(1→。336型糖是不含O-乙酰化的β-连接己糖胺[12、13]，其与抗336菌株(ATCC 55804)的抗体交叉反应。典型的组合是5型和8型糖，可将336型糖加入该配对[14]。The conjugate used in component (2) of the combination includes a sugar moiety and a carrier moiety. The sugar moiety is derived from the capsular sugar of Staphylococcus aureus. The sugars may be polysaccharides, the size of which arises during the purification of bacterial capsular sugars, or may be oligosaccharides obtained by fragmenting such polysaccharides. Capsular saccharides can be obtained from any suitable strain of S. aureus (or any bacterium with similar or identical saccharides), for example from S. aureus strains type 5 and/or 8 and/or S. aureus strain type 336 . Most strains of infectious S. aureus contain type 5 or type 8 capsular saccharides. Both have FucNAcp and ManNAcA in their repeat units, which can be used to introduce sulfhydryl groups for attachment. The repeat unit of sugar type 5 is →4)-β-D-ManNAcA-(1→4)-α-L-FucNAc(3OAc)-(1→3)-β-D-FucNAc-(1→, while 8 The repeating unit of sugar type is →3)-β-D-ManNAcA(4OAc)-(1→3)-α-L-FucNAc(1→3)-α-D-FucNAc(1→. Type 336 sugar is not Contains O-acetylated β-linked hexosamines [12, 13] which cross-react with antibodies against the 336 strain (ATCC 55804). Typical combinations are type 5 and type 8 sugars to which type 336 sugars can be added Pairing [14].

本发明还提供包含以下组合的免疫原性组合物：The present invention also provides immunogenic compositions comprising the combination of:

(1)选自第一、第二、第三或第四抗原组的一种或多种抗原；(1) one or more antigens selected from the first, second, third or fourth antigen group;

(2)金黄色葡萄球菌表多糖和载体蛋白的一种或多种偶联物；和(2) one or more conjugates of S. aureus exopolysaccharide and carrier protein; and

(3)金黄色葡萄球菌荚膜糖和载体蛋白的一种或多种偶联物。(3) One or more conjugates of Staphylococcus aureus capsular saccharide and carrier protein.

这些偶联物中的载体部分通常是蛋白质，但通常不是(1)中的抗原之一。典型的载体蛋白是细菌毒素，如白喉或破伤风毒素，或者其类毒素或突变体或片段。CRM197白喉毒素突变体是有用的[15]。其它合适的载体蛋白包括脑膜炎奈瑟球菌(N.meningitidis)外膜蛋白复合物[16]、合成肽[17，18]、热激蛋白[19，20]、百日咳蛋白[21，22]、细胞因子[23]、淋巴因子[23]、激素[23]、生长因子[23]、包含多种来自各种病原体衍生抗原的人CD4+T细胞表位的人工蛋白[24]如N19[25]、流感嗜血杆菌的蛋白D[26-28]、肺炎球菌溶血素[29]或其无毒衍生物[30]、肺炎球菌表面蛋白PspA[31]、摄铁蛋白[32]、来自艰难梭菌(C.difficile)的毒素A或B[33]、重组铜绿假单胞菌(P.aeruginosa)胞外蛋白A(rEPA)[34]等。在一些实施方式中，所述载体蛋白是金黄色葡萄球菌蛋白，例如选自第一、第二、第三或第四抗原组的抗原。The carrier moiety in these conjugates is usually a protein, but usually not one of the antigens in (1). Typical carrier proteins are bacterial toxins, such as diphtheria or tetanus toxins, or toxoids or mutants or fragments thereof. The CRM197 diphtheria toxin mutant is useful [15]. Other suitable carrier proteins include N. meningitidis outer membrane protein complex [16], synthetic peptides [17, 18], heat shock proteins [19, 20], pertussis proteins [21, 22], Cytokines[23], lymphokines[23], hormones[23], growth factors[23], artificial proteins containing various human CD4 + T cell epitopes from various pathogen-derived antigens[24] such as N19[25 ], protein D of Haemophilus influenzae[26-28], pneumolysin[29] or its non-toxic derivatives[30], pneumococcal surface protein PspA[31], ferritin[32], from difficile Clostridium (C.difficile) toxin A or B [33], recombinant Pseudomonas aeruginosa (P.aeruginosa) extracellular protein A (rEPA) [34] and so on. In some embodiments, the carrier protein is a Staphylococcus aureus protein, eg, an antigen selected from the first, second, third or fourth antigen group.

如果组合物包含一种以上偶联物，各偶联物可利用相同或不同的载体蛋白。If the composition comprises more than one conjugate, each conjugate may utilize the same or a different carrier protein.

偶联物可具有过量载体(w/w)或过量糖(w/w)。在一些实施方式中，偶联物可包含相同重量的载体和糖。Conjugates may have excess carrier (w/w) or excess sugar (w/w). In some embodiments, the conjugate may comprise the same weight of carrier and sugar.

载体分子可直接与载体共价偶联，或通过接头偶联。可通过(例如)糖和载体之间的还原胺化(如参考文献35和36所述)，实现与蛋白质的直接连接。首先需要通过，例如氧化活化糖。可用任何已知方法，如参考文献37和38所述的方法通过接头基团进行连接。优选的连接类型是己二酸接头，其可通过以下方式形成：将游离-NH2基团(如通过胺化引入葡聚糖中)与己二酸偶联(例如，利用二酰亚胺活化)，然后将蛋白质偶联于所得的糖-己二酸中间体[39，40]。另一种优选连接形式是羰基接头，这种连接可通过以下方式形成：使糖CDI的游离羟基发生反应[41，42]，然后与蛋白质反应形成氨基甲酸酯连接。其它接头包括β-丙酰胺基[43]、硝基苯基-乙胺[44]、卤代酰基卤化物[45]、糖苷键[46]、6-氨基己酸[47]、ADH[48]、C4到C12部分[49]等。也采用碳二亚胺缩合反应[50]。The carrier molecule can be covalently coupled directly to the carrier, or via a linker. Direct linkage to proteins can be achieved, for example, by reductive amination between a sugar and a carrier (as described in refs 35 and 36). First, the sugar needs to be activated by, for example, oxidation. Linkage via a linker group can be accomplished by any known method, such as those described in references 37 and 38. The preferred type of linkage is an adipic acid linker, which can be formed by coupling a free -NH2 group (e.g., into dextran by amination) to adipic acid (e.g., using imide-activated ), followed by coupling of proteins to the resulting sugar-adipate intermediate [39,40]. Another preferred form of attachment is the carbonyl linker, which can be formed by reacting the free hydroxyl groups of the sugar CDI [41, 42] followed by reaction with the protein to form a carbamate linkage. Other linkers include β-propionamido [43], nitrophenyl-ethylamine [44], haloacyl halides [45], glycosidic linkages [46], 6-aminocaproic acid [47], ADH [48 ], C 4 to C 12 parts [49], etc. The carbodiimide condensation reaction was also employed [50].

可采用各种方式制备PNAG偶联物，例如通过包括以下步骤的方法：a)加入包含马来酰亚胺基团的接头来活化PNAG以形成活化的PNAG；b)加入包含巯基的接头来活化载体蛋白以形成活化的载体蛋白；和c)使活化的PNAG与活化的载体蛋白反应形成PNAG-载体蛋白偶联物；或通过包括以下步骤的方法：a)加入包含巯基的接头来活化PNAG以形成活化的PNAG；b)加入包含马来酰亚胺基团的接头来活化载体蛋白以形成活化的载体蛋白；和c)使活化的PNAG与活化的载体蛋白反应形成PNAG-载体蛋白偶联物；或通过包括以下步骤的方法：a)加入包含巯基的接头来活化PNAG以形成活化的PNAG；b)加入包含巯基的接头来活化载体蛋白以形成活化的载体蛋白；和c)使活化的PNAG与活化的载体蛋白反应形成PNAG-载体蛋白偶联物。PNAG conjugates can be prepared in various ways, for example by a method comprising: a) adding a linker comprising a maleimide group to activate PNAG to form activated PNAG; b) adding a linker comprising a sulfhydryl group to activate carrier protein to form an activated carrier protein; and c) reacting activated PNAG with an activated carrier protein to form a PNAG-carrier protein conjugate; or by a method comprising the steps of: a) adding a linker comprising a sulfhydryl group to activate PNAG to forming activated PNAG; b) adding a linker comprising a maleimide group to activate the carrier protein to form an activated carrier protein; and c) reacting the activated PNAG with the activated carrier protein to form a PNAG-carrier protein conjugate or by a method comprising the steps of: a) adding a linker comprising a sulfhydryl group to activate PNAG to form activated PNAG; b) adding a linker comprising a sulfhydryl group to activate a carrier protein to form an activated carrier protein; and c) making activated PNAG React with activated carrier protein to form PNAG-carrier protein conjugate.

本发明抗原组中鉴定的各抗原可用作表多糖的载体蛋白，以形成共价偶联物。因此，本发明提供一种免疫原性组合物，其包含(1)选自第一、第二、第三或第四抗原组的抗原和(2)金黄色葡萄球菌表多糖的偶联物。本发明还提供一种免疫原性组合物，其包含(1)选自第一、第二、第三或第四抗原组的抗原和(2)金黄色葡萄球菌荚膜糖的偶联物。此类偶联物的其它特征如上所述。这些偶联物可与本文所述的任何抗原联用。Each of the antigens identified in the group of antigens of the present invention can be used as a carrier protein for exopolysaccharides to form covalent conjugates. Accordingly, the present invention provides an immunogenic composition comprising (1) an antigen selected from the first, second, third or fourth antigen group and (2) a conjugate of Staphylococcus aureus exopolysaccharide. The present invention also provides an immunogenic composition comprising (1) an antigen selected from the first, second, third or fourth antigen group and (2) a conjugate of Staphylococcus aureus capsular saccharide. Other features of such conjugates are as described above. These conjugates can be used in conjunction with any of the antigens described herein.

与非葡萄球菌抗原组合Combined with non-staphylococcal antigens

本发明抗原组中鉴定的各抗原可与非葡萄球菌抗原，特别是与医院内感染相关细菌的抗原联用。本发明提供一种包含以下组合的免疫原性组合物：Each of the antigens identified in the panel of antigens of the present invention may be used in combination with non-staphylococcal antigens, particularly antigens from bacteria associated with nosocomial infections. The present invention provides an immunogenic composition comprising the combination of:

(1)选自第一、第二、第三或第四抗原组(如上所述)的一种或多种抗原；和(1) one or more antigens selected from the first, second, third or fourth antigen group (as described above); and

(2)一种或多种选自下组的抗原：艰难梭菌(Clostridium difficile)、铜绿假单胞菌(Pseudomonas aeruginosa)、白色念珠菌(Candida albicans)；和肠外病原性大肠杆菌(Escherichia coli)。(2) One or more antigens selected from the group consisting of Clostridium difficile, Pseudomonas aeruginosa, Candida albicans; and extraintestinal pathogenic Escherichia coli (Escherichia coli).

与本发明葡萄球菌抗原联用的其它合适抗原列于参考文献51第33-46页。Other suitable antigens for use in combination with the staphylococcal antigens of the invention are listed on pages 33-46 of reference 51.

第一抗原组first antigen group

clfAclfA

“clfA”抗原注释为“凝聚因子(clumping factor)A”。在NCTC 8325菌株中，clfA是SAOUHSC_00812，具有氨基酸序列SEQ ID NO：1(GI：88194572)。在Newman菌株中，其是nwmn_0756(GI：151220968)。The "clfA" antigen is annotated as "clumping factor A". In the NCTC 8325 strain, clfA is SAOUHSC_00812, which has the amino acid sequence of SEQ ID NO: 1 (GI: 88194572). In the Newman strain it is nwmn_0756 (GI: 151220968).

有用的clfA抗原能引发识别SEQ ID NO：1的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：1有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：1的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些clfA蛋白包括SEQ ID NO：1的变体。(b)的优选片段包含来自SEQ ID NO：1的表位。其它优选片段缺少SEQID NO：1的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：1的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：1的至少一个表位。SEQ ID NO：1的最后368个C-末端氨基酸可有用地省去。SEQ ID NO：1的前39个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful clfA antigens are capable of eliciting antibodies that recognize SEQ ID NO: 1 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 1 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 1, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These clfA proteins include variants of SEQ ID NO:1. A preferred fragment of (b) comprises an epitope from SEQ ID NO:1. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 1 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 1, and At least one epitope of SEQ ID NO: 1 is retained. The last 368 C-terminal amino acids of SEQ ID NO: 1 can be usefully omitted. The first 39 N-terminal amino acids of SEQ ID NO: 1 can be usefully omitted. Other fragments omit one or more protein domains.

SEQ ID NO：224是SEQ ID NO：1的有用片段(‘ClfA40-559’)。该片段省去了对着SEQ ID NO：1的C-末端的长重复区域。SEQ ID NO: 224 is a useful fragment of SEQ ID NO: 1 ('ClfA 40-559 '). This fragment omits the long repeat region towards the C-terminus of SEQ ID NO:1.

clfBcfB

“clfB”抗原注释为“凝聚因子B”。在NCTC 8325菌株中，clfB是SAOUHSC_02963，具有氨基酸序列SEQ ID NO：2(GI：88196585)。在Newman菌株中，其是nwmn_2529(GI：151222741)。The "clfB" antigen is annotated as "clotting factor B". In NCTC 8325 strain, clfB is SAOUHSC_02963, which has the amino acid sequence of SEQ ID NO: 2 (GI: 88196585). In the Newman strain it is nwmn_2529 (GI: 151222741 ).

有用的clfB抗原能引发识别SEQ ID NO：2的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：2有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：2的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些clfB蛋白包括SEQ ID NO：2的变体。(b)的优选片段包含来自SEQ ID NO：2的表位。其它优选片段缺少SEQID NO：2的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：2的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：2的至少一个表位。SEQ ID NO：2的最后40个C-末端氨基酸通常可省去。SEQ ID NO：2的前44个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。ClfB天然是长蛋白质，因此，利用片段有助于，例如纯化、操作、融合、表达等等。Useful clfB antigens are capable of eliciting antibodies that recognize SEQ ID NO: 2 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 2 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 2, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These clfB proteins include variants of SEQ ID NO:2. A preferred fragment of (b) comprises an epitope from SEQ ID NO:2. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 2 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 2, and At least one epitope of SEQ ID NO:2 is retained. The last 40 C-terminal amino acids of SEQ ID NO: 2 can usually be omitted. The first 44 N-terminal amino acids of SEQ ID NO: 2 can be usefully omitted. Other fragments omit one or more protein domains. CIfB is naturally a long protein, therefore, the use of fragments facilitates, eg, purification, manipulation, fusion, expression, and the like.

SEQ ID NO：163是SEQ ID NO：2的有用片段(‘ClfB45-552’)。该片段包含ClfB中最暴露的结构域，更易用于工业水平。其还降低抗原与人蛋白的相似性。依据ClfB的3-结构域模型的其它有用片段包括：ClfB45-360(也称为CLfB-N12；SEQ ID NO：196)；ClfB212-542(也称为CLfB-N23；SEQ ID NO：197)；和ClfB360-542(也称为CLfB-N3；SEQ ID NO：198)。SEQ ID NO: 163 is a useful fragment of SEQ ID NO: 2 ('ClfB 45-552 '). This fragment contains the most exposed domain in ClfB and is easier to use at industrial level. It also reduces the similarity of the antigen to human proteins. Other useful fragments based on the 3-domain model of CIfB include: CIfB 45-360 (also known as CLfB-N12; SEQ ID NO: 196); CIfB 212-542 (also known as CLfB-N23; SEQ ID NO: 197 ); and CIfB 360-542 (also known as CLfB-N3; SEQ ID NO: 198).

coAcoA

“coA”抗原注释为“凝固酶Coa”。在NCTC 8325菌株中，coA是SAOUHSC_00192，具有氨基酸序列SEQ ID NO：3(GI：88194002)。在Newman菌株中，其是nwmn_0166(GI：151220378)。The "coA" antigen is annotated as "Coagulase Coa". In the NCTC 8325 strain, the coA is SAOUHSC_00192 with the amino acid sequence of SEQ ID NO: 3 (GI: 88194002). In the Newman strain it is nwmn_0166 (GI: 151220378).

有用的coA抗原能引发识别SEQ ID NO：3的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：3有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：3的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些coA蛋白包括SEQ ID NO：3的变体。(b)的优选片段包含来自SEQ ID NO：3的表位。其它优选片段缺少SEQID NO：3的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：3的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：3的至少一个表位。SEQ ID NO：3的前14个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful coA antigens are capable of eliciting antibodies that recognize SEQ ID NO:3 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:3 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 3, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These coA proteins include variants of SEQ ID NO:3. A preferred fragment of (b) comprises an epitope from SEQ ID NO:3. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 3 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 3, and At least one epitope of SEQ ID NO:3 is retained. The first 14 N-terminal amino acids of SEQ ID NO: 3 can be usefully omitted. Other fragments omit one or more protein domains.

eapeap

“eap”抗原注释为“II类MHC类似物蛋白”。在NCTC 8325菌株中，eap是SAOUHSC_02161，具有氨基酸序列SEQ ID NO：4(GI：88195840)。在Newman菌株中，其是nwmn_1872(GI：151222084)。The "eap" antigen is annotated as "MHC class II analog protein". In the NCTC 8325 strain, the eap is SAOUHSC_02161 with the amino acid sequence of SEQ ID NO: 4 (GI: 88195840). In the Newman strain it is nwmn_1872 (GI: 151222084).

有用的eap抗原能引发识别SEQ ID NO：4的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：4有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：4的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些eap蛋白包括SEQ ID NO：4的变体。(b)的优选片段包含来自SEQ ID NO：4的表位。其它优选片段缺少SEQID NO：4的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：4的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：4的至少一个表位。SEQ ID NO：4的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful eap antigens can elicit antibodies that recognize SEQ ID NO:4 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:4 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 4, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These eap proteins include variants of SEQ ID NO:4. A preferred fragment of (b) comprises an epitope from SEQ ID NO:4. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 4 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 4, and At least one epitope of SEQ ID NO:4 is retained. The first 17 N-terminal amino acids of SEQ ID NO: 4 can be usefully omitted. Other fragments omit one or more protein domains.

ebhAebA

“ebhA”抗原注释为“EbhA”。在NCTC 8325菌株中，ebhA是SAOUHSC_01447，具有氨基酸序列SEQ ID NO：5(GI：88195168)。The "ebhA" antigen is annotated as "EbhA". In NCTC 8325 strain, ebhA is SAOUHSC_01447, which has the amino acid sequence of SEQ ID NO: 5 (GI: 88195168).

有用的ebhA抗原能引发识别SEQ ID NO：5的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：5有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：5的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些ebhA蛋白包括SEQ ID NO：5的变体。(b)的优选片段包含来自SEQ ID NO：5的表位。其它优选片段缺少SEQID NO：5的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：5的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：5的至少一个表位。SEQ ID NO：5的前39个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful ebhA antigens are capable of eliciting antibodies that recognize SEQ ID NO:5 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:5 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 5, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These ebhA proteins include variants of SEQ ID NO:5. A preferred fragment of (b) comprises an epitope from SEQ ID NO:5. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 5 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 5, and At least one epitope of SEQ ID NO:5 is retained. The first 39 N-terminal amino acids of SEQ ID NO: 5 can be usefully omitted. Other fragments omit one or more protein domains.

ebpSEBP

“ebpS”抗原注释为“弹性蛋白结合蛋白EbpS”。在NCTC 8325菌株中，ebpS是SAOUHSC_01501，具有氨基酸序列SEQ ID NO：6(GI：88195217)。在Newman菌株中，其是nwmn_1389(GI：151221601)。The "ebpS" antigen is annotated as "Elastin-binding protein EbpS". In NCTC 8325 strain, ebpS is SAOUHSC_01501 with amino acid sequence SEQ ID NO: 6 (GI: 88195217). In the Newman strain it is nwmn_1389 (GI: 151221601 ).

有用的ebpS抗原能引发识别SEQ ID NO：6的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：6有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：6的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些ebpS蛋白包括SEQ ID NO：6的变体。(b)的优选片段包含来自SEQ ID NO：6的表位。其它优选片段缺少SEQID NO：6的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：6的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：6的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful ebpS antigens are capable of eliciting antibodies that recognize SEQ ID NO: 6 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 6 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 6, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These ebpS proteins include variants of SEQ ID NO:6. A preferred fragment of (b) comprises an epitope from SEQ ID NO:6. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 6 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 6, and At least one epitope of SEQ ID NO:6 is retained. Other fragments omit one or more protein domains.

SEQ ID NO：165是SEQ ID NO：6的有用片段(‘EbpS1-198’)。该片段包含EbpS中最暴露的结构域，更易用于工业水平。其还降低抗原与人蛋白的相似性。SEQ ID NO: 165 is a useful fragment of SEQ ID NO: 6 ('EbpS 1-198 '). This fragment contains the most exposed domain in EbpS and is easier to use at industrial level. It also reduces the similarity of the antigen to human proteins.

efbefb

“efb”抗原注释为“截短的纤维蛋白原结合蛋白”。在NCTC 8325菌株中，efb是SAOUHSC_01114，具有氨基酸序列SEQ ID NO：7(GI：88194860)。在Newman菌株中，其是nwmn_1069(GI：151221281)。The "efb" antigen is annotated as "truncated fibrinogen binding protein". In NCTC 8325 strain, efb is SAOUHSC_01114, which has the amino acid sequence of SEQ ID NO: 7 (GI: 88194860). In the Newman strain it is nwmn_1069 (GI: 151221281 ).

有用的efb抗原能引发识别SEQ ID NO：7的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：7有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：7的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些efb蛋白包括SEQ ID NO：7的变体。(b)的优选片段包含来自SEQ ID NO：7的表位。其它优选片段缺少SEQ ID NO：7的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：7的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：7的至少一个表位。SEQ ID NO：7的前14个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful efb antigens are capable of eliciting antibodies that recognize SEQ ID NO: 7 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 7 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 7, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These efb proteins include variants of SEQ ID NO:7. A preferred fragment of (b) comprises an epitope from SEQ ID NO:7. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 7 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 7, while retaining at least one epitope of SEQ ID NO:7. The first 14 N-terminal amino acids of SEQ ID NO: 7 can be usefully omitted. Other fragments omit one or more protein domains.

empemp

“emp”抗原注释为“胞外基质和血浆结合蛋白”。在NCTC 8325菌株中，emp是SAOUHSC_00816，具有氨基酸序列SEQ ID NO：8(GI：88194575)。在Newman菌株中，其是nwmn_0758(GI：151220970)。The "emp" antigen is annotated as "extracellular matrix and plasma-bound protein". In the NCTC 8325 strain, the emp is SAOUHSC_00816, having the amino acid sequence of SEQ ID NO: 8 (GI: 88194575). In the Newman strain it is nwmn_0758 (GI: 151220970).

有用的emp抗原能引发识别SEQ ID NO：8的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：8有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：8的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些emp蛋白包括SEQ ID NO：8的变体。(b)的优选片段包含来自SEQ ID NO：8的表位。其它优选片段缺少SEQID NO：8的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：8的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：8的至少一个表位。SEQ ID NO：8的前26个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful emp antigens are capable of eliciting antibodies that recognize SEQ ID NO:8 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:8 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 8, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These emp proteins include variants of SEQ ID NO:8. A preferred fragment of (b) comprises an epitope from SEQ ID NO:8. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 8 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 8, and At least one epitope of SEQ ID NO:8 is retained. The first 26 N-terminal amino acids of SEQ ID NO: 8 can be usefully omitted. Other fragments omit one or more protein domains.

SEQ ID NO：190、191、192和193是SEQ ID NO：8的有用片段(分别是‘Emp35-340’、‘Emp27-334’、‘Emp35-334’和‘Emp27-147’)。SEQ ID NO: 190, 191, 192 and 193 are useful fragments of SEQ ID NO: 8 ('Emp 35-340 ', 'Emp 27-334 ', 'Emp 35-334 ' and 'Emp 27-147 ' respectively ).

esaCesaC

“esaC”抗原注释为“esaC”。在NCTC 8325菌株中，esaC是SAOUHSC_00264，具有氨基酸序列SEQ ID NO：9(GI：88194069)。The "esaC" antigen is annotated as "esaC". In NCTC 8325 strain, esaC is SAOUHSC_00264 with amino acid sequence SEQ ID NO: 9 (GI: 88194069).

有用的esaC抗原能引发识别SEQ ID NO：9的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：9有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：9的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些esaC蛋白包括SEQ ID NO：9的变体。(b)的优选片段包含来自SEQ ID NO：9的表位。其它优选片段缺少SEQ ID NO：9的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：9的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：9的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful esaC antigens are capable of eliciting antibodies that recognize SEQ ID NO: 9 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 9 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 9, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These esaC proteins include variants of SEQ ID NO:9. A preferred fragment of (b) comprises an epitope from SEQ ID NO:9. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 9 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 9, While retaining at least one epitope of SEQ ID NO:9. Other fragments omit one or more protein domains.

esxAesxA

“esxA”抗原注释为“蛋白质”。在NCTC 8325菌株中，esxA是SAOUHSC_00257，具有氨基酸序列SEQ ID NO：10(GI：88194063)。The "esxA" antigen is annotated as "protein". In NCTC 8325 strain, esxA is SAOUHSC_00257 with amino acid sequence SEQ ID NO: 10 (GI: 88194063).

有用的esxA抗原能引发识别SEQ ID NO：10的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：10有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：10的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90或更高)。这些esxA蛋白包括SEQ ID NO：10的变体。(b)的优选片段包含来自SEQ ID NO：10的表位。其它优选片段缺少SEQ ID NO：10的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：10的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：10的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful esxA antigens are capable of eliciting antibodies that recognize SEQ ID NO: 10 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 10 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 10, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90 or higher). These esxA proteins include variants of SEQ ID NO:10. A preferred fragment of (b) comprises an epitope from SEQ ID NO:10. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 10 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 10, While retaining at least one epitope of SEQ ID NO: 10. Other fragments omit one or more protein domains.

esxBwxya

“esxB”抗原注释为“esxB”。在NCTC 8325菌株中，esxB是SAOUHSC_00265，具有氨基酸序列SEQ ID NO：11(GI：88194070)。The "esxB" antigen is annotated as "esxB". In NCTC 8325 strain, esxB is SAOUHSC_00265 with amino acid sequence SEQ ID NO: 11 (GI: 88194070).

有用的esxB抗原能引发识别SEQ ID NO：11的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：11有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：11的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些esxB蛋白包括SEQ ID NO：11的变体。(b)的优选片段包含来自SEQ ID NO：11的表位。其它优选片段缺少SEQ ID NO：11的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：11的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：11的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful esxB antigens are capable of eliciting antibodies that recognize SEQ ID NO: 11 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 11 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 11, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These esxB proteins include variants of SEQ ID NO:11. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 11. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 11 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 11, While retaining at least one epitope of SEQ ID NO: 11. Other fragments omit one or more protein domains.

FnBAFnBA

“FnBA”抗原注释为“纤连蛋白-结合蛋白A前体FnBPA”。在NCTC8325菌株中，FnBA是SAOUHSC_02803，具有氨基酸序列SEQ ID NO：12(GI：88196438)。在Newman菌株中，其是nwmn_2399(GI：151222611)。蛋白质组分析揭示该蛋白质是分泌或表面暴露的蛋白。The "FnBA" antigen is annotated as "fibronectin-binding protein A precursor FnBPA". In the NCTC8325 strain, the FnBA is SAOUHSC_02803, which has the amino acid sequence of SEQ ID NO: 12 (GI: 88196438). In the Newman strain it is nwmn_2399 (GI: 151222611 ). Proteome analysis revealed that the protein was secreted or surface exposed.

有用的FnBA抗原能引发识别SEQ ID NO：12的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：12有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：12的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些FnBA蛋白包括SEQ ID NO：12的变体。(b)的优选片段包含来自SEQ ID NO：12的表位。其它优选片段缺少SEQ ID NO：12的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：12的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：12的至少一个表位。SEQ ID NO：12的最后37个C-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。FnBA天然是长蛋白质，因此，利用片段有助于，例如纯化、操作、融合、表达等等。Useful FnBA antigens are capable of eliciting antibodies that recognize SEQ ID NO: 12 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 12 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 12, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These FnBA proteins include variants of SEQ ID NO:12. A preferred fragment of (b) comprises an epitope from SEQ ID NO:12. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 12 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 12, While retaining at least one epitope of SEQ ID NO: 12. The last 37 C-terminal amino acids of SEQ ID NO: 12 can be usefully omitted. Other fragments omit one or more protein domains. FnBA is naturally a long protein, therefore, the use of fragments facilitates, eg, purification, manipulation, fusion, expression, and the like.

SEQ ID NO：166(‘FnBA1-511’)和167(‘FnBA512-953’)是SEQ ID NO：12的有用片段。这些片段更易在工业水平使用。SEQ ID NO: 166 ('FnBA 1-511 ') and 167 ('FnBA 512-953 ') are useful fragments of SEQ ID NO:12. These fragments are easier to use at an industrial level.

FnBBFnBB

“FnBB”抗原注释为“纤连蛋白-结合蛋白B前体FnBPB”。在NCTC8325菌株中，FnBA是SAOUHSC_02802，具有氨基酸序列SEQ ID NO：13(GI：88196437)。在Newman菌株中，其是nwmn_2397(GI：151222609)。The "FnBB" antigen is annotated as "fibronectin-binding protein B precursor FnBPB". In the NCTC8325 strain, the FnBA is SAOUHSC_02802, which has the amino acid sequence of SEQ ID NO: 13 (GI: 88196437). In the Newman strain it is nwmn_2397 (GI: 151222609).

有用的FnBB抗原能引发识别SEQ ID NO：13的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：13有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：13的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些FnBA蛋白包括SEQ ID NO：13的变体。(b)的优选片段包含来自SEQ ID NO：13的表位。其它优选片段缺少SEQ ID NO：13的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：13的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：13的至少一个表位。SEQ ID NO：13的最后37个C-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful FnBB antigens are capable of eliciting antibodies that recognize SEQ ID NO: 13 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 13 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 13, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These FnBA proteins include variants of SEQ ID NO:13. A preferred fragment of (b) comprises an epitope from SEQ ID NO:13. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 13 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 13, While retaining at least one epitope of SEQ ID NO: 13. The last 37 C-terminal amino acids of SEQ ID NO: 13 can be usefully omitted. Other fragments omit one or more protein domains.

HlaHla

“Hla”抗原是“α-溶血素前体”，也称为“α毒素”或简称为“溶血素”。在NCTC 8325菌株中，Hla是SAOUHSC_01121，具有氨基酸序列SEQ ID NO：14(GI：88194865)。在Newman菌株中，其是nwmn_1073(GI：151221285)。Hla是大多数金黄色葡萄球菌菌株产生的重要毒力决定因素，其具有成孔和溶血活性。动物模型中，抗-Hla抗体可中和该毒素的有害作用，Hla尤其可用于保护免遭肺炎。"Hla" antigen is "alpha-hemolysin precursor", also known as "alpha toxin" or simply "hemolysin". In the NCTC 8325 strain, Hla is SAOUHSC_01121, having the amino acid sequence of SEQ ID NO: 14 (GI: 88194865). In the Newman strain it is nwmn_1073 (GI: 151221285). Hla is an important virulence determinant produced by most S. aureus strains, with pore-forming and hemolytic activities. In animal models, anti-Hla antibodies can neutralize the deleterious effects of the toxin, and HIa in particular can be used to protect against pneumonia.

有用的Hla抗原能引发识别SEQ ID NO：14的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：14有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：14的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些Hla蛋白包括SEQ ID NO：14的变体。(b)的优选片段包含来自SEQ ID NO：14的表位。其它优选片段缺少SEQ ID NO：14的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：14的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：14的至少一个表位。SEQ ID NO：14的前26个N-末端氨基酸可有用地省去(例如，得到SEQ ID NO：231)。还可采用C-末端截短，例如仅留下50个氨基酸(SEQ ID NO：14的残基27-76)[52]。其它片段省去一个或多个蛋白质结构域。Useful Hla antigens can elicit antibodies that recognize SEQ ID NO: 14 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 14 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 14, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These HIa proteins include variants of SEQ ID NO:14. A preferred fragment of (b) comprises an epitope from SEQ ID NO:14. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 14 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 14, While retaining at least one epitope of SEQ ID NO: 14. The first 26 N-terminal amino acids of SEQ ID NO: 14 can be usefully omitted (e.g., resulting in SEQ ID NO: 231). C-terminal truncations may also be employed, for example leaving only 50 amino acids (residues 27-76 of SEQ ID NO: 14) [52]. Other fragments omit one or more protein domains.

可通过化学灭活(例如，利用甲醛、戊二醛或其它交联剂)避免本发明组合物中Hla的毒性。然而，优选利用Hla的突变形式除去其毒性而保留其免疫原性。本领域已知此类脱毒突变体。一种有用的Hla抗原在SEQ ID NO：14的残基61(成熟抗原的残基35)处具有突变(即，省去前26个N-末端氨基酸后＝SEQ ID NO：231的残基35)。因此，残基61可以不是组氨酸，反而可以是，例如Ile、Val或优选Leu。还可在该位置采用His-Arg突变。例如，SEQ ID NO：150是成熟的突变型Hla-H35L序列(即，含H35L突变的SEQ ID NO：231)，有用的Hla抗原包含SEQ ID NO：150。另一有用的突变用较短的序列替换长环，例如用四聚体，如PSGS(SEQ ID NO：225)替换SEQ ID NO：14的残基136-174处的39聚体，例如SEQ ID NO：189(其还包含H35L突变)和SEQID NO：216(其不含H35L突变)中所示的。另一有用的突变用，例如亮氨酸替代残基Y101(SEQ ID NO：242)。另一有用的突变用，例如亮氨酸替代残基D152(SEQ ID NO：243)。另一有用的突变用，例如亮氨酸替代残基H35和Y101(SEQ ID NO：244)。另一有用的突变用，例如亮氨酸替代残基H35和D152(SEQ ID NO：245)。Toxicity of HIa in compositions of the invention can be avoided by chemical inactivation (eg, using formaldehyde, glutaraldehyde or other cross-linking agents). However, it is preferred to utilize a mutated form of HIa to remove its toxicity while retaining its immunogenicity. Such detoxified mutants are known in the art. A useful Hla antigen has a mutation at residue 61 of SEQ ID NO: 14 (residue 35 of the mature antigen) (i.e. after omission of the first 26 N-terminal amino acids = residue 35 of SEQ ID NO: 231 ). Thus, instead of histidine, residue 61 may be, for example, Ile, Val or preferably Leu. A His-Arg mutation can also be employed at this position. For example, SEQ ID NO: 150 is a mature mutant Hla-H35L sequence (i.e., SEQ ID NO: 231 containing the H35L mutation), and useful Hla antigens comprise SEQ ID NO: 150. Another useful mutation replaces the long loop with a shorter sequence, for example replacing the 39mer at residues 136-174 of SEQ ID NO: 14 with a tetramer, such as PSGS (SEQ ID NO: 225), such as SEQ ID NO: 225 Shown in NO: 189 (it also comprises H35L mutation) and SEQID NO: 216 (it does not contain H35L mutation). Another useful mutation replaces residue Y101 with, for example, leucine (SEQ ID NO: 242). Another useful mutation replaces residue D152 (SEQ ID NO: 243) with, for example, leucine. Another useful mutation replaces residues H35 and Y101 with, for example, leucine (SEQ ID NO: 244). Another useful mutation replaces residues H35 and D152 with, for example, leucine (SEQ ID NO: 245).

其它有用的Hla抗原公开于参考文献53和54。Other useful HIa antigens are disclosed in references 53 and 54.

SEQ ID NO：160、161和194是SEQ ID NO：14的3个有用片段(分别是‘Hla27-76’、‘Hla27-89’和‘Hla27-79’)。SEQ ID NO：158、159和195是SEQ IDNO：150的相应片段。SEQ ID NO: 160, 161 and 194 are 3 useful fragments of SEQ ID NO: 14 ('Hla 27-76 ', 'Hla 27-89 ' and 'Hla 27-79 ', respectively). SEQ ID NO:158, 159 and 195 are corresponding fragments of SEQ ID NO:150.

一个有用的Hla序列是实施例中所用的SEQ ID NO：232。其具有N-末端Met，然后是来自表达载体的Ala-Ser二肽，其后是SEQ ID NO：150(来自NCTC8325菌株)。其由SEQ ID NO：233编码。A useful HIa sequence is SEQ ID NO: 232 used in the Examples. It has an N-terminal Met, followed by the Ala-Ser dipeptide from the expression vector, followed by SEQ ID NO: 150 (from NCTC8325 strain). It is encoded by SEQ ID NO:233.

hlgBwxya

“hlgB”抗原注释为“杀白细胞素f亚单位前体HlgB”。在NCTC 8325菌株中，hlgB是SAOUHSC_02710，具有氨基酸序列SEQ ID NO：15(GI：88196350)。The "hlgB" antigen is annotated as "leukocidin f subunit precursor HlgB". In NCTC 8325 strain, hlgB is SAOUHSC_02710, which has the amino acid sequence of SEQ ID NO: 15 (GI: 88196350).

有用的hlgB抗原能引发识别SEQ ID NO：15的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：15有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：15的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些hlgB蛋白包括SEQ ID NO：15的变体。(b)的优选片段包含来自SEQ ID NO：15的表位。其它优选片段缺少SEQ ID NO：15的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：15的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：15的至少一个表位。SEQ ID NO：15的前26个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful hlgB antigens are capable of eliciting antibodies that recognize SEQ ID NO: 15 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 15 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 15, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These hlgB proteins include variants of SEQ ID NO:15. A preferred fragment of (b) comprises an epitope from SEQ ID NO:15. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 15 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 15, while retaining at least one epitope of SEQ ID NO: 15. The first 26 N-terminal amino acids of SEQ ID NO: 15 can be usefully omitted. Other fragments omit one or more protein domains.

hlgCwxya

“hlgC”抗原注释为“杀白细胞素s亚单位前体HlgC”。在NCTC 8325菌株中，hlgC是SAOUHSC_02709，具有氨基酸序列SEQ ID NO：16(GI：88196349)。The "hlgC" antigen is annotated as "leukocidin S subunit precursor HlgC". In NCTC 8325 strain, hlgC is SAOUHSC_02709, which has the amino acid sequence of SEQ ID NO: 16 (GI: 88196349).

有用的hlgC抗原能引发识别SEQ ID NO：16的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：16有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：16的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些hlgC蛋白包括SEQ ID NO：16的变体。(b)的优选片段包含来自SEQ ID NO：16的表位。其它优选片段缺少SEQ ID NO：16的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：16的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：16的至少一个表位。SEQ ID NO：16的前29个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful hlgC antigens are capable of eliciting antibodies that recognize SEQ ID NO: 16 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 16 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 16, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These hlgC proteins include variants of SEQ ID NO:16. A preferred fragment of (b) comprises an epitope from SEQ ID NO:16. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 16 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 16, While retaining at least one epitope of SEQ ID NO: 16. The first 29 N-terminal amino acids of SEQ ID NO: 16 can be usefully omitted. Other fragments omit one or more protein domains.

isdAisA

“isdA”抗原注释为“IsdA蛋白”。在NCTC 8325菌株中，isdA是SAOUHSC_01081，具有氨基酸序列SEQ ID NO：17(GI：88194829)。在Newman菌株中，其是nwmn_1041(GI：151221253)。The "isdA" antigen is annotated as "IsdA protein". In NCTC 8325 strain, isdA is SAOUHSC_01081 with amino acid sequence SEQ ID NO: 17 (GI: 88194829). In the Newman strain it is nwmn_1041 (GI: 151221253).

有用的isdA抗原能引发识别SEQ ID NO：17的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：17有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：17的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些isdA蛋白包括SEQ ID NO：17的变体。(b)的优选片段包含来自SEQ ID NO：17的表位。其它优选片段缺少SEQ ID NO：17的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：17的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：17的至少一个表位。SEQ ID NO：17的最后38个C-末端氨基酸可有用地省去。SEQ ID NO：17的前46个N-末端氨基酸可有用地省去。还可采用截短以排除SEQ ID NO：17的C-末端38聚体(始于LPKTG基序)。其它片段省去一个或多个蛋白质结构域。Useful isdA antigens are capable of eliciting antibodies that recognize SEQ ID NO: 17 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 17 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 17, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These isdA proteins include variants of SEQ ID NO:17. A preferred fragment of (b) comprises an epitope from SEQ ID NO:17. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 17 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 17, while retaining at least one epitope of SEQ ID NO: 17. The last 38 C-terminal amino acids of SEQ ID NO: 17 can be usefully omitted. The first 46 N-terminal amino acids of SEQ ID NO: 17 can be usefully omitted. Truncations may also be employed to exclude the C-terminal 38-mer of SEQ ID NO: 17 (beginning with the LPKTG motif). Other fragments omit one or more protein domains.

SEQ ID NO：157是SEQ ID NO：17的有用片段(SEQ ID NO：17的氨基酸40-184；‘IsdA40-184’)，其包括天然蛋白质的血红素结合位点，还包括抗原的最暴露结构域。其还降低抗原与人蛋白质的相似性。其它有用的片段公开于参考文献55和56。SEQ ID NO: 157 is a useful fragment of SEQ ID NO: 17 (amino acids 40-184 of SEQ ID NO: 17; 'IsdA 40-184 '), which includes the heme binding site of the native protein and also includes the most exposed domain. It also reduces the similarity of the antigen to human proteins. Other useful fragments are disclosed in references 55 and 56.

IsdA不能良好吸附于氢氧化铝佐剂，因此组合物中存在的IsdA可以是不吸附的或可吸附于其它佐剂，例如吸附于磷酸铝。IsdA does not adsorb well to aluminum hydroxide adjuvants, so the IsdA present in the composition may be unadsorbed or adsorbable to other adjuvants, such as to aluminum phosphate.

抗-IsdA抗体保护小鼠以免金黄色葡萄球菌脓肿形成和免遭致死性攻击[57]。Anti-IsdA antibodies protected mice from S. aureus abscess formation and from lethal challenge [57].

isdBisdB

“isdB”抗原注释为“神经丝蛋白isdB”。在NCTC 8325菌株中，isdB是SAOUHSC_01079，具有氨基酸序列SEQ ID NO：18(GI：88194828)。有人提出IsdB本身可用作疫苗抗原[2]，但该疫苗可能不能预防肺炎。The "isdB" antigen is annotated as "neurofilament protein isdB". In the NCTC 8325 strain, isdB is SAOUHSC_01079, having the amino acid sequence of SEQ ID NO: 18 (GI: 88194828). It has been suggested that IsdB itself could be used as a vaccine antigen [2], but the vaccine may not protect against pneumonia.

有用的isdB抗原能引发识别SEQ ID NO：18的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：18有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：18的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些isdB蛋白包括SEQ ID NO：18的变体。(b)的优选片段包含来自SEQ ID NO：18的表位。其它优选片段缺少SEQ ID NO：18的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：18的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：18的至少一个表位。SEQ ID NO：18的最后36个C-末端氨基酸可有用地省去。SEQ ID NO：18的前40个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。IsdB的有用片段公开于参考文献56和58，例如缺少SEQ ID NO：18的37个内部氨基酸。Useful isdB antigens can elicit antibodies that recognize SEQ ID NO: 18 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 18 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 18, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These isdB proteins include variants of SEQ ID NO: 18. A preferred fragment of (b) comprises an epitope from SEQ ID NO:18. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 18 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 18, While retaining at least one epitope of SEQ ID NO: 18. The last 36 C-terminal amino acids of SEQ ID NO: 18 can be usefully omitted. The first 40 N-terminal amino acids of SEQ ID NO: 18 can be usefully omitted. Other fragments omit one or more protein domains. Useful fragments of IsdB are disclosed in references 56 and 58, for example lacking the 37 internal amino acids of SEQ ID NO:18.

抗-IsdB抗体保护小鼠以免金黄色葡萄球菌脓肿形成和免遭致死性攻击[57]。Anti-IsdB antibodies protected mice from S. aureus abscess formation and from lethal challenge [57].

在一些实施方式中，本发明的组合物不包含isdB抗原。In some embodiments, the compositions of the invention do not comprise an isdB antigen.

IsdCIsdC

“isdC”抗原注释为“蛋白质”。在NCTC 8325菌株中，isdC是SAOUHSC_01082，具有氨基酸序列SEQ ID NO：19(GI：88194830)。The "isdC" antigen is annotated as "protein". In the NCTC 8325 strain, isdC is SAOUHSC_01082, which has the amino acid sequence of SEQ ID NO: 19 (GI: 88194830).

有用的isdC抗原能引发识别SEQ ID NO：19的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：19有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：19的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些isdC蛋白包括SEQ ID NO：19的变体。(b)的优选片段包含来自SEQ ID NO：19的表位。其它优选片段缺少SEQID NO：19的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：19的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：19的至少一个表位。SEQ ID NO：19的最后39个C-末端氨基酸可有用地省去。SEQ ID NO：19的前28个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。IsdB的有用片段公开于参考文献56。Useful isdC antigens are capable of eliciting antibodies recognizing SEQ ID NO: 19 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 19 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 19, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These isdC proteins include variants of SEQ ID NO:19. A preferred fragment of (b) comprises an epitope from SEQ ID NO:19. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 19 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 19, and At least one epitope of SEQ ID NO: 19 is retained. The last 39 C-terminal amino acids of SEQ ID NO: 19 can be usefully omitted. The first 28 N-terminal amino acids of SEQ ID NO: 19 can be usefully omitted. Other fragments omit one or more protein domains. Useful fragments of IsdB are disclosed in ref. 56.

参考文献59公开了有用地包含IsdB和IsdH的表位的抗原。Reference 59 discloses antigens usefully comprising epitopes of IsdB and IsdH.

isdGisG

“isdG”抗原注释为“血红素-降解性单加氧酶IsdG”。在NCTC 8325菌株中，isdG是SAOUHSC_01089，具有氨基酸序列SEQ ID NO：20(GI：88194836)。The "isdG" antigen is annotated as "heme-degrading monooxygenase IsdG". In the NCTC 8325 strain, isdG is SAOUHSC_01089, which has the amino acid sequence of SEQ ID NO: 20 (GI: 88194836).

有用的isdG抗原能引发识别SEQ ID NO：20的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：20有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：20的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些isdG蛋白包括SEQ ID NO：20的变体。(b)的优选片段包含来自SEQ ID NO：20的表位。其它优选片段缺少SEQ ID NO：20的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：20的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：20的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful isdG antigens are capable of eliciting antibodies that recognize SEQ ID NO: 20 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 20 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 20, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These isdG proteins include variants of SEQ ID NO:20. A preferred fragment of (b) comprises an epitope from SEQ ID NO:20. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 20 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 20, while retaining at least one epitope of SEQ ID NO: 20. Other fragments omit one or more protein domains.

isdHisH

“isdH”抗原注释为“IsdH”。在NCTC 8325菌株中，isdH是SAOUHSC_01843，具有氨基酸序列SEQ ID NO：21(GI：88195542)。在Newman菌株中，其是nwmn_1624(GI：151221836)。其还称为HarA。The "isdH" antigen is annotated as "IsdH". In the NCTC 8325 strain, isdH is SAOUHSC_01843, which has the amino acid sequence of SEQ ID NO: 21 (GI: 88195542). In the Newman strain it is nwmn_1624 (GI: 151221836). It is also known as HarA.

有用的isdH抗原能引发识别SEQ ID NO：21的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：21有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：21的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些isdH蛋白包括SEQ ID NO：21的变体。(b)的优选片段包含来自SEQ ID NO：21的表位。其它优选片段缺少SEQ ID NO：21的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：21的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：21的至少一个表位。SEQ ID NO：21的最后35个C-末端氨基酸可有用地省去。SEQ ID NO：21的前40个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful isdH antigens are capable of eliciting antibodies that recognize SEQ ID NO: 21 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 21 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 21, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These isdH proteins include variants of SEQ ID NO:21. A preferred fragment of (b) comprises an epitope from SEQ ID NO:21. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 21 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 21, while retaining at least one epitope of SEQ ID NO: 21. The last 35 C-terminal amino acids of SEQ ID NO: 21 can be usefully omitted. The first 40 N-terminal amino acids of SEQ ID NO: 21 can be usefully omitted. Other fragments omit one or more protein domains.

参考文献59公开了有用地包含IsdB和IsdH的表位的抗原。Reference 59 discloses antigens usefully comprising epitopes of IsdB and IsdH.

isdIisI

“isdI”抗原注释为“血红素-降解性单加氧酶IsdI”。在NCTC 8325菌株中，isdI是SAOUHSC_00130，具有氨基酸序列SEQ ID NO：22(GI：88193943)。The "isdl" antigen is annotated as "heme-degrading monooxygenase Isdl". In NCTC 8325 strain, isdI is SAOUHSC_00130, having the amino acid sequence of SEQ ID NO: 22 (GI: 88193943).

有用的isdI抗原能引发识别SEQ ID NO：22的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：22有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：22的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些isdI蛋白包括SEQ ID NO：22的变体。(b)的优选片段包含来自SEQ ID NO：22的表位。其它优选片段缺少SEQ ID NO：22的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：22的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：22的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful isdI antigens are capable of eliciting antibodies that recognize SEQ ID NO: 22 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 22 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 22, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These isdl proteins include variants of SEQ ID NO:22. A preferred fragment of (b) comprises an epitope from SEQ ID NO:22. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 22 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 22, While retaining at least one epitope of SEQ ID NO: 22. Other fragments omit one or more protein domains.

lukDlukD

“lukD”抗原注释为“白细胞毒素LukD”。在NCTC 8325菌株中，lukD是SAOUHSC_01954，具有氨基酸序列SEQ ID NO：23(GI：88195647)。在Newman菌株中，其是nwmn_1718(GI：151221930)。The "lukD" antigen is annotated as "leukotoxin LukD". In the NCTC 8325 strain, lukD is SAOUHSC_01954, which has the amino acid sequence of SEQ ID NO: 23 (GI: 88195647). In the Newman strain it is nwmn_1718 (GI: 151221930).

有用的lukD抗原能引发识别SEQ ID NO：23的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：23有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：23的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些lukD蛋白包括SEQ ID NO：23的变体。(b)的优选片段包含来自SEQ ID NO：23的表位。其它优选片段缺少SEQ ID NO：23的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：23的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：23的至少一个表位。SEQ ID NO：23的最后43个C-末端氨基酸可有用地省去。SEQ ID NO：23的前26个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful lukD antigens are capable of eliciting antibodies that recognize SEQ ID NO: 23 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 23 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 23, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These lukD proteins include variants of SEQ ID NO:23. A preferred fragment of (b) comprises an epitope from SEQ ID NO:23. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 23 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 23, While retaining at least one epitope of SEQ ID NO: 23. The last 43 C-terminal amino acids of SEQ ID NO: 23 can be usefully omitted. The first 26 N-terminal amino acids of SEQ ID NO: 23 can be usefully omitted. Other fragments omit one or more protein domains.

lukEluke

“lukE”抗原注释为“白细胞毒素LukE”。在NCTC 8325菌株中，lukE是SAOUHSC_01955，具有氨基酸序列SEQ ID NO：24(GI：88195648)。The "lukE" antigen is annotated as "leukotoxin LukE". In NCTC 8325 strain, lukE is SAOUHSC_01955, which has the amino acid sequence of SEQ ID NO: 24 (GI: 88195648).

有用的lukE抗原能引发识别SEQ ID NO：24的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：24有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：24的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些lukE蛋白包括SEQ ID NO：24的变体。(b)的优选片段包含来自SEQ ID NO：24的表位。其它优选片段缺少SEQ ID NO：24的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：24的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：24的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful lukE antigens are capable of eliciting antibodies that recognize SEQ ID NO: 24 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 24 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 24, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These lukE proteins include variants of SEQ ID NO:24. A preferred fragment of (b) comprises an epitope from SEQ ID NO:24. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 24 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 24, while retaining at least one epitope of SEQ ID NO: 24. Other fragments omit one or more protein domains.

lukFlukF

“lukF”抗原注释为“杀白细胞素/溶血素毒素家族LukF”。在NCTC8325菌株中，lukF是SAOUHSC_02241，具有氨基酸序列SEQ ID NO：25(GI：88195914)。The "lukF" antigen is annotated as "Leukocidin/Hemolysin Toxin Family LukF". In the NCTC8325 strain, lukF is SAOUHSC_02241, which has the amino acid sequence of SEQ ID NO: 25 (GI: 88195914).

有用的lukF抗原能引发识别SEQ ID NO：25的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：25有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：25的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些lukF蛋白包括SEQ ID NO：25的变体。(b)的优选片段包含来自SEQ ID NO：25的表位。其它优选片段缺少SEQ ID NO：25的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：25的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：25的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful lukF antigens are capable of eliciting antibodies that recognize SEQ ID NO: 25 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 25 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 25, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These lukF proteins include variants of SEQ ID NO:25. A preferred fragment of (b) comprises an epitope from SEQ ID NO:25. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 25 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 25, while retaining at least one epitope of SEQ ID NO: 25. Other fragments omit one or more protein domains.

lukSlukS

“lukS”抗原注释为“可能的杀白细胞素S亚单位LukS”。在NCTC 8325菌株中，lukS是SAOUHSC_02243，具有氨基酸序列SEQ ID NO：26(GI：88195915)。在Newman菌株中，其是nwmn_1928(GI：151222140)。The "lukS" antigen is annotated as "probable leukocidin S subunit LukS". In NCTC 8325 strain, lukS is SAOUHSC_02243, which has the amino acid sequence of SEQ ID NO: 26 (GI: 88195915). In the Newman strain it is nwmn_1928 (GI: 151222140).

有用的lukS抗原能引发识别SEQ ID NO：26的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：26有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：26的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些lukS蛋白包括SEQ ID NO：26的变体。(b)的优选片段包含来自SEQ ID NO：26的表位。其它优选片段缺少SEQ ID NO：26的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：26的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：26的至少一个表位。SEQ ID NO：26的前22个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。A useful lukS antigen is capable of eliciting antibodies recognizing SEQ ID NO: 26 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 26 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 26, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These lukS proteins include variants of SEQ ID NO:26. A preferred fragment of (b) comprises an epitope from SEQ ID NO:26. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 26 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 26, While retaining at least one epitope of SEQ ID NO: 26. The first 22 N-terminal amino acids of SEQ ID NO: 26 can be usefully omitted. Other fragments omit one or more protein domains.

nucnuc

“nuc”抗原注释为“热核酸酶前体”。在NCTC 8325菌株中，nuc是SAOUHSC_01316，具有氨基酸序列SEQ ID NO：27(GI：88195046)。The "nuc" antigen is annotated as "thermonuclease precursor". In the NCTC 8325 strain, the nuc is SAOUHSC_01316, which has the amino acid sequence of SEQ ID NO: 27 (GI: 88195046).

有用的nuc抗原能引发识别SEQ ID NO：27的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：27有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：27的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些nuc蛋白包括SEQ ID NO：27的变体。(b)的优选片段包含来自SEQ ID NO：27的表位。其它优选片段缺少SEQ ID NO：27的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：27的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：27的至少一个表位。SEQ ID NO：27的最后39个C-末端氨基酸可有用地省去。SEQ ID NO：27的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful nuc antigens are capable of eliciting antibodies that recognize SEQ ID NO: 27 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 27 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 27, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These nuc proteins include variants of SEQ ID NO:27. A preferred fragment of (b) comprises an epitope from SEQ ID NO:27. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 27 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 27, while retaining at least one epitope of SEQ ID NO: 27. The last 39 C-terminal amino acids of SEQ ID NO: 27 can be usefully omitted. The first 19 N-terminal amino acids of SEQ ID NO: 27 can be usefully omitted. Other fragments omit one or more protein domains.

sasAsasA

“sasA”抗原注释为“SasA”。在NCTC 8325菌株中，sasA是SAOUHSC_02990，具有氨基酸序列SEQ ID NO：28(GI：88196609)。The "sasA" antigen is annotated as "SasA". In the NCTC 8325 strain, sasA is SAOUHSC_02990, which has the amino acid sequence of SEQ ID NO: 28 (GI: 88196609).

有用的sasA抗原能引发识别SEQ ID NO：28的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：28有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：28的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sasA蛋白包括SEQ ID NO：28的变体。(b)的优选片段包含来自SEQ ID NO：28的表位。其它优选片段缺少SEQ ID NO：28的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：28的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：28的至少一个表位。SEQ ID NO：28的最后43个C-末端氨基酸可有用地省去。SEQ ID NO：28的前90个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sasA antigens can elicit antibodies that recognize SEQ ID NO: 28 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 28 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 28, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sasA proteins include variants of SEQ ID NO:28. A preferred fragment of (b) comprises an epitope from SEQ ID NO:28. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 28 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 28, While retaining at least one epitope of SEQ ID NO: 28. The last 43 C-terminal amino acids of SEQ ID NO: 28 can be usefully omitted. The first 90 N-terminal amino acids of SEQ ID NO: 28 can be usefully omitted. Other fragments omit one or more protein domains.

sasBsasB

“sasB”抗原注释为“fmtB蛋白；SasB”。在NCTC 8325菌株中，sasB是SAOUHSC_02404，具有氨基酸序列SEQ ID NO：29(GI：88196065)。The "sasB" antigen is annotated as "fmtB protein; SasB". In the NCTC 8325 strain, sasB is SAOUHSC_02404, which has the amino acid sequence of SEQ ID NO: 29 (GI: 88196065).

有用的sasB抗原能引发识别SEQ ID NO：29的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：29有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：29的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sasB蛋白包括SEQ ID NO：29的变体。(b)的优选片段包含来自SEQ ID NO：29的表位。其它优选片段缺少SEQ ID NO：29的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：29的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：29的至少一个表位。SEQ ID NO：29的最后39个C-末端氨基酸可有用地省去。SEQ ID NO：29的前38个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。A useful sasB antigen is capable of eliciting antibodies recognizing SEQ ID NO: 29 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 29 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 29, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sasB proteins include variants of SEQ ID NO:29. A preferred fragment of (b) comprises an epitope from SEQ ID NO:29. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 29 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 29, While retaining at least one epitope of SEQ ID NO: 29. The last 39 C-terminal amino acids of SEQ ID NO: 29 can be usefully omitted. The first 38 N-terminal amino acids of SEQ ID NO: 29 can be usefully omitted. Other fragments omit one or more protein domains.

sasCsasC

“sasC”抗原注释为“Mrp蛋白；SasC”。在NCTC 8325菌株中，sasC是SAOUHSC_01873，具有氨基酸序列SEQ ID NO：30(GI：88195570)。The "sasC" antigen is annotated as "Mrp protein; SasC". In the NCTC 8325 strain, sasC is SAOUHSC_01873, which has the amino acid sequence of SEQ ID NO: 30 (GI: 88195570).

有用的sasC抗原能引发识别SEQ ID NO：30的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：30有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：30的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sasC蛋白包括SEQ ID NO：30的变体。(b)的优选片段包含来自SEQ ID NO：30的表位。其它优选片段缺少SEQ ID NO：30的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：30的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：30的至少一个表位。SEQ ID NO：30的最后36个C-末端氨基酸可有用地省去。SEQ ID NO：30的前37个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sasC antigens are capable of eliciting antibodies that recognize SEQ ID NO: 30 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 30 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 30, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sasC proteins include variants of SEQ ID NO:30. A preferred fragment of (b) comprises an epitope from SEQ ID NO:30. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 30 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 30, while retaining at least one epitope of SEQ ID NO:30. The last 36 C-terminal amino acids of SEQ ID NO: 30 can be usefully omitted. The first 37 N-terminal amino acids of SEQ ID NO: 30 can be usefully omitted. Other fragments omit one or more protein domains.

sasDsasD

“sasD”抗原注释为“SasD蛋白”。在NCTC 8325菌株中，sasD是SAOUHSC_00094，具有氨基酸序列SEQ ID NO：31(GI：88193909)。The "sasD" antigen is annotated as "SasD protein". In the NCTC 8325 strain, sasD is SAOUHSC_00094, which has the amino acid sequence of SEQ ID NO: 31 (GI: 88193909).

有用的sasD抗原能引发识别SEQ ID NO：31的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：31有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：31的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sasD蛋白包括SEQ ID NO：31的变体。(b)的优选片段包含来自SEQ ID NO：31的表位。其它优选片段缺少SEQ ID NO：31的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：31的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：31的至少一个表位。SEQ ID NO：31的前28个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sasD antigens can elicit antibodies that recognize SEQ ID NO: 31 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 31 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 31, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sasD proteins include variants of SEQ ID NO:31. A preferred fragment of (b) comprises an epitope from SEQ ID NO:31. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 31 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 31, While retaining at least one epitope of SEQ ID NO: 31. The first 28 N-terminal amino acids of SEQ ID NO: 31 can be usefully omitted. Other fragments omit one or more protein domains.

sasFsasF

“sasF”抗原注释为“SasF蛋白”。在NCTC 8325菌株中，sasF是SAOUHSC_02982，具有氨基酸序列SEQ ID NO：32(GI：88196601)。The "sasF" antigen is annotated as "SasF protein". In the NCTC 8325 strain, sasF is SAOUHSC_02982, which has the amino acid sequence of SEQ ID NO: 32 (GI: 88196601).

有用的sasF抗原能引发识别SEQ ID NO：32的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：32有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：32的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sasF蛋白包括SEQ ID NO：32的变体。(b)的优选片段包含来自SEQ ID NO：32的表位。其它优选片段缺少SEQ ID NO：32的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：32的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：32的至少一个表位。SEQ ID NO：32的最后39个C-末端氨基酸可有用地省去。SEQ ID NO：32的前37个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sasF antigens are capable of eliciting antibodies that recognize SEQ ID NO: 32 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 32 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 32, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sasF proteins include variants of SEQ ID NO:32. A preferred fragment of (b) comprises an epitope from SEQ ID NO:32. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 32 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 32, While retaining at least one epitope of SEQ ID NO: 32. The last 39 C-terminal amino acids of SEQ ID NO: 32 can be usefully omitted. The first 37 N-terminal amino acids of SEQ ID NO: 32 can be usefully omitted. Other fragments omit one or more protein domains.

sdrCsdrC

“sdrC”抗原注释为“sdrC蛋白”。在NCTC 8325菌株中，sdrC是SAOUHSC_00544，具有氨基酸序列SEQ ID NO：33(GI：88194324)。The "sdrC" antigen is annotated as "sdrC protein". In NCTC 8325 strain, sdrC is SAOUHSC_00544 with amino acid sequence SEQ ID NO: 33 (GI: 88194324).

有用的sdrC抗原能引发识别SEQ ID NO：33的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：33有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：33的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sdrC蛋白包括SEQ ID NO：33的变体。(b)的优选片段包含来自SEQ ID NO：33的表位。其它优选片段缺少SEQ ID NO：33的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：33的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：33的至少一个表位。SEQ ID NO：33的最后38个C-末端氨基酸可有用地省去。SEQ ID NO：33的前50个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。SdrC天然是长蛋白质，因此，利用片段有助于，例如纯化、操作、融合、表达等等。Useful sdrC antigens are capable of eliciting antibodies that recognize SEQ ID NO: 33 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 33 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 33, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sdrC proteins include variants of SEQ ID NO:33. A preferred fragment of (b) comprises an epitope from SEQ ID NO:33. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 33 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 33, While retaining at least one epitope of SEQ ID NO: 33. The last 38 C-terminal amino acids of SEQ ID NO: 33 can be usefully omitted. The first 50 N-terminal amino acids of SEQ ID NO: 33 can be usefully omitted. Other fragments omit one or more protein domains. SdrC is naturally a long protein, therefore, the use of fragments facilitates, eg, purification, manipulation, fusion, expression, and the like.

SEQ ID NO：164是SEQ ID NO：33的有用片段(‘SdrC51-518’)。该片段包含SdrC的最暴露结构域，更易在工业水平使用。其还降低抗原与人蛋白质的相似性。SEQ ID NO: 164 is a useful fragment of SEQ ID NO: 33 ('SdrC5 1-518 '). This fragment contains the most exposed domain of SdrC and is easier to use at industrial level. It also reduces the similarity of the antigen to human proteins.

sdrDsdrD

“sdrD”抗原注释为“sdrD蛋白”。在NCTC 8325菌株中，sdrD是SAOUHSC_00545，具有氨基酸序列SEQ ID NO：34(GI：88194325)。The "sdrD" antigen is annotated as "sdrD protein". In the NCTC 8325 strain, sdrD is SAOUHSC_00545, which has the amino acid sequence of SEQ ID NO: 34 (GI: 88194325).

有用的sdrD抗原能引发识别SEQ ID NO：34的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：34有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：34的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sdrD蛋白包括SEQ ID NO：34的变体。(b)的优选片段包含来自SEQ ID NO：34的表位。其它优选片段缺少SEQ ID NO：34的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：34的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：34的至少一个表位。SEQ ID NO：34的最后38个C-末端氨基酸可有用地省去。SEQ ID NO：34的前52个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。SdrD天然是长蛋白质，因此，利用片段有助于，例如纯化、操作、融合、表达等等。Useful sdrD antigens are capable of eliciting antibodies that recognize SEQ ID NO: 34 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 34 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 34, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sdrD proteins include variants of SEQ ID NO:34. A preferred fragment of (b) comprises an epitope from SEQ ID NO:34. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 34 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 34, While retaining at least one epitope of SEQ ID NO: 34. The last 38 C-terminal amino acids of SEQ ID NO: 34 can be usefully omitted. The first 52 N-terminal amino acids of SEQ ID NO: 34 can be usefully omitted. Other fragments omit one or more protein domains. SdrD is naturally a long protein, therefore, the use of fragments facilitates, eg, purification, manipulation, fusion, expression, and the like.

SEQ ID NO：156是SEQ ID NO：34的有用片段(‘SdrD53-592’)。该片段包含SdrD的最暴露结构域，更易在工业水平使用。其还降低抗原与人蛋白质的相似性。具有相同C-末端残基的另一有用片段是SdrD394-592(也称为SdrD-N3；SEQ ID NO：199)。另一有用片段是SEQ ID NO：236(SEQ ID NO：34的氨基酸593-1123)，本文称为‘SdrDCnaB’。SEQ ID NO: 156 is a useful fragment of SEQ ID NO: 34 ('SdrD 53-592 '). This fragment contains the most exposed domain of SdrD and is easier to use at industrial level. It also reduces the similarity of the antigen to human proteins. Another useful fragment with the same C-terminal residues is SdrD 394-592 (also known as SdrD-N3; SEQ ID NO: 199). Another useful fragment is SEQ ID NO: 236 (amino acids 593-1123 of SEQ ID NO: 34), referred to herein as 'SdrD CnaB '.

sdrE2sdrE2

“sdrE2”抗原注释为“富含Ser-Asp的纤维蛋白原/骨唾液蛋白-结合蛋白SdrE”。在Newman菌株中，sdrE2是NWMN_0525，具有氨基酸序列SEQ ID NO：35(GI：151220737)。The "sdrE2" antigen is annotated as "Ser-Asp-rich fibrinogen/bone sialoprotein-binding protein SdrE". In the Newman strain, sdrE2 is NWMN_0525, having the amino acid sequence of SEQ ID NO: 35 (GI: 151220737).

有用的sdrE2抗原能引发识别SEQ ID NO：35的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：35有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：35的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sdrE2蛋白包括SEQ ID NO：35的变体。(b)的优选片段包含来自SEQ ID NO：35的表位。其它优选片段缺少SEQ ID NO：35的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：35的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：35的至少一个表位。SEQ ID NO：35的最后38个C-末端氨基酸可有用地省去。SEQ ID NO：35的前52个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。SdrE2天然是长蛋白质，因此，利用片段有助于，例如纯化、操作、融合、表达等等。Useful sdrE2 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 35 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 35 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 35, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sdrE2 proteins include variants of SEQ ID NO:35. A preferred fragment of (b) comprises an epitope from SEQ ID NO:35. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 35 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 35, while retaining at least one epitope of SEQ ID NO:35. The last 38 C-terminal amino acids of SEQ ID NO: 35 can be usefully omitted. The first 52 N-terminal amino acids of SEQ ID NO: 35 can be usefully omitted. Other fragments omit one or more protein domains. SdrE2 is naturally a long protein, therefore, the use of fragments facilitates, eg, purification, manipulation, fusion, expression, and the like.

SEQ ID NO：155是SEQ ID NO：35的有用片段(‘SdrE53-632’)。该片段包含SdrE2的最暴露结构域，更易在工业水平使用。其还降低抗原与人蛋白质的相似性。SEQ ID NO: 155 is a useful fragment of SEQ ID NO: 35 ('SdrE 53-632 '). This fragment contains the most exposed domain of SdrE2 and is easier to use at industrial level. It also reduces the similarity of the antigen to human proteins.

spaspa

“spa”抗原注释为“蛋白A”或“Spa”。在NCTC 8325菌株中，spa是SAOUHSC_00069，具有氨基酸序列SEQ ID NO：36(GI：88193885)。在Newman菌株中，其是nwmn_0055(GI：151220267)。所有金黄色葡萄球菌菌株表达spa的结构基因，其是充分表征的毒力因子，其细胞壁-锚定表面蛋白产物具有5个高度同源性的免疫球蛋白结合域，称为E、D、A、B和C[60]。这些结构域在氨基酸水平显示约80％相同性，长度为56-61个残基，组织成串联重复[61]。SpA合成为含N-末端信号肽和C-末端分选信号的前体蛋白[62、63]。细胞壁锚定spa在葡萄球菌表面极其丰富地展示[64、65]。其免疫球蛋白结合域各自由组装成三螺旋束(three helix bundle)的反平行α-螺旋构成，并能结合免疫球蛋白G(IgG)的Fc结构域[66、67]、IgM的VH3重链(Fab)(即，B细胞受体)[68]、血管假性血友病因子的A1结构域[69]和/或TNF-α受体I(TNFRI)[70]，其展示在气道上皮的表面。The "spa" antigen is annotated as "Protein A" or "Spa". In the NCTC 8325 strain, spa is SAOUHSC_00069, having the amino acid sequence of SEQ ID NO: 36 (GI: 88193885). In the Newman strain it is nwmn_0055 (GI: 151220267). All S. aureus strains express the structural gene for spa, a well-characterized virulence factor, and its cell wall-anchored surface protein product has five highly homologous immunoglobulin-binding domains called E, D, A , B, and C [60]. These domains show approximately 80% identity at the amino acid level, are 56–61 residues in length, and are organized as tandem repeats [61]. SpA is synthesized as a precursor protein containing an N-terminal signal peptide and a C-terminal sorting signal [62, 63]. Cell wall-anchored spas are extremely abundantly displayed on the surface of staphylococci [64, 65]. Each of its immunoglobulin binding domains is composed of antiparallel α-helices assembled into a three helix bundle, and can bind the Fc domain of immunoglobulin G (IgG) [66, 67], the VH3 heavy of IgM chain (Fab) (i.e., B-cell receptor) [68], the A1 domain of von Willebrand factor [69] and/or TNF-α receptor I (TNFRI) [70], which are demonstrated in surface of the epithelium.

有用的spa抗原能引发识别SEQ ID NO：36的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：36有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：36的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些spa蛋白包括SEQ ID NO：36的变体。(b)的优选片段包含来自SEQ ID NO：36的表位。其它优选片段缺少SEQ ID NO：36的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：36的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：36的至少一个表位。SEQ ID NO：36的最后35个C-末端氨基酸可有用地省去。SEQ ID NO：36的前36个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。参考文献71提示各IgG-结合域可单独或组合用作免疫原。Useful spa antigens can elicit antibodies that recognize SEQ ID NO: 36 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 36 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 36, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These spa proteins include variants of SEQ ID NO:36. A preferred fragment of (b) comprises an epitope from SEQ ID NO:36. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 36 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 36, While retaining at least one epitope of SEQ ID NO: 36. The last 35 C-terminal amino acids of SEQ ID NO: 36 can be usefully omitted. The first 36 N-terminal amino acids of SEQ ID NO: 36 can be usefully omitted. Other fragments omit one or more protein domains. Reference 71 suggests that IgG-binding domains can be used alone or in combination as immunogens.

SEQ ID NO：162是SEQ ID NO：36的有用片段(‘Spa37-325’)。该片段含有所有5个SpA Ig-结合域(从N-到C-末端的天然排列顺序是E、D、A、B、C)，包括SpA最暴露的结构域。其还降低抗原与人蛋白质的相似性。其它有用的片段可省去天然A、B、C、D和/或E结构域中的1、2、3或4个以防止过度B细胞扩增和随后的凋亡，如果spa起到B细胞超抗原的作用可能发生该情况。如参考文献71报道的，其它有用的片段可仅包含天然A、B、C、D和/或E结构域中的1、2、3或4个，例如仅包含SpA(A)结构域而不含B到E，或仅包含SpA(D)结构域而不含A、B、C或E，等等。因此，本发明所用的spa抗原可包含1、2、3、4或5个IgG-结合域，但最好具有4个或更少。SEQ ID NO: 162 is a useful fragment of SEQ ID NO: 36 ('Spa 37-325 '). This fragment contains all 5 SpA Ig-binding domains (N- to C-terminus in natural order E, D, A, B, C), including the most exposed domain of SpA. It also reduces the similarity of the antigen to human proteins. Other useful fragments can omit 1, 2, 3 or 4 of the native A, B, C, D and/or E domains to prevent excessive B cell expansion and subsequent apoptosis if spa functions as a B cell This may occur through the action of superantigens. As reported in ref. 71, other useful fragments may comprise only 1, 2, 3 or 4 of the native A, B, C, D and/or E domains, e.g. only the SpA(A) domain and not Contains B to E, or only the SpA(D) domain without A, B, C or E, etc. Thus, spa antigens used in the present invention may comprise 1, 2, 3, 4 or 5 IgG-binding domains, but preferably have 4 or less.

如果抗原仅包含一类spa结构域(例如，仅是Spa(A)或Spa(D)结构域)，其可包含多于一个拷贝的该结构域，例如一条多肽链中包含多个SpA(D)结构域。If the antigen contains only one type of spa domain (e.g., only Spa(A) or Spa(D) domains), it may contain more than one copy of this domain, e.g., multiple SpA(D) domains in one polypeptide chain. ) domain.

与SEQ ID NO：36相比，该抗原内的各结构域可在1、2、3、4、5、6、7、8、9、10或更多个氨基酸处突变(例如，参见参考文献71，其公开了在结构域D的残基3和/或24，结构域A的残基46和/或53处的突变，等等)。此类突变不应使得抗原不能引发识别SEQ ID NO：36的抗体，但可造成抗原不结合IgG和/或其它人蛋白(例如，人血液蛋白)。Each domain within the antigen may be mutated at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more amino acids compared to SEQ ID NO: 36 (e.g., see ref. 71, which discloses mutations at residues 3 and/or 24 of domain D, residues 46 and/or 53 of domain A, etc.). Such mutations should not render the antigen incapable of eliciting antibodies that recognize SEQ ID NO: 36, but may result in the antigen not binding IgG and/or other human proteins (e.g., human blood proteins).

在某些方面，spa抗原包含以下取代：(a)SpA结构域A、B、C、D和/或E的IgG Fc结合亚域中的一个或多个氨基酸取代，从而破坏和/或降低与IgG Fc的结合，和(b)SpA结构域A、B、C、D和/或E的VH3结合亚域中的一个或多个氨基酸取代，从而破坏和/或降低与VH3的结合。在某些实施方式中，变体SpA包含最少或最多1、2、3、4、5、6、7、8、9、10或更多个变体SpA结构域D肽。In certain aspects, the spa antigen comprises the following substitutions: (a) one or more amino acid substitutions in the IgG Fc-binding subdomains of SpA domains A, B, C, D and/or E, thereby disrupting and/or reducing interaction with IgG Fc binding, and (b) one or more amino acid substitutions in the VH3 binding subdomains of SpA domains A, B, C, D and/or E, thereby disrupting and/or reducing binding to VH3 combined. In certain embodiments, the variant SpA comprises a minimum or a maximum of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more variant SpA domain D peptides.

第二抗原组Second antigen group

sta001sta001

“sta001”抗原注释为“5-核苷酸酶家族蛋白”。在NCTC 8325菌株中，sta001是SAOUHSC_00025，具有氨基酸序列SEQ ID NO：37(GI：88193846)。在Newman菌株中，其是nwmn_0022(GI：151220234)。其还称为AdsA和SasH及SA0024。The "sta001" antigen is annotated as "5-nucleotidase family protein". Among the NCTC 8325 strains, sta001 is SAOUHSC_00025, which has the amino acid sequence of SEQ ID NO: 37 (GI: 88193846). In the Newman strain it is nwmn_0022 (GI: 151220234). It is also known as AdsA and SasH and SA0024.

有用的sta001抗原能引发识别SEQ ID NO：37的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：37有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：37的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta001蛋白包括SEQ ID NO：37的变体。(b)的优选片段包含来自SEQ ID NO：37的表位。其它优选片段缺少SEQ ID NO：37的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：36的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：37的至少一个表位。SEQ ID NO：37的最后34个C-末端氨基酸可有用地省去。SEQ ID NO：37的前38个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta001 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 37 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 37 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 37, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta001 proteins include variants of SEQ ID NO:37. A preferred fragment of (b) comprises an epitope from SEQ ID NO:37. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 37 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 36, While retaining at least one epitope of SEQ ID NO: 37. The last 34 C-terminal amino acids of SEQ ID NO: 37 can be usefully omitted. The first 38 N-terminal amino acids of SEQ ID NO: 37 can be usefully omitted. Other fragments omit one or more protein domains.

sta002sta002

“sta002”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta002是SAOUHSC_00356，具有氨基酸序列SEQ ID NO：38(GI：88194155)。在Newman菌株中，其是nwmn_0364(GI：151220576)。The "sta002" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta002 is SAOUHSC_00356, which has the amino acid sequence of SEQ ID NO: 38 (GI: 88194155). In the Newman strain it is nwmn_0364 (GI: 151220576).

有用的sta002抗原能引发识别SEQ ID NO：38的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：38有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：38的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta002蛋白包括SEQ ID NO：38的变体。(b)的优选片段包含来自SEQ ID NO：38的表位。其它优选片段缺少SEQ IDNO：38的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：38的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ IDNO：38的至少一个表位。SEQ ID NO：38的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta002 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 38 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 38 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 38, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta002 proteins include variants of SEQ ID NO:38. A preferred fragment of (b) comprises an epitope from SEQ ID NO:38. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 38 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 38, and At least one epitope of SEQ ID NO: 38 is retained. The first 18 N-terminal amino acids of SEQ ID NO: 38 can be usefully omitted. Other fragments omit one or more protein domains.

SEQ ID NO：153(‘sta00219-187’)和154(‘sta00219-124’)是SEQ ID NO：38的两个有用片段，其降低抗原与人蛋白质的相似性。SEQ ID NO: 153 ('sta002 19-187 ') and 154 ('sta002 19-124 ') are two useful fragments of SEQ ID NO: 38 that reduce the similarity of the antigen to the human protein.

sta003sta003

“sta003”抗原注释为“表面蛋白”。在NCTC 8325菌株中，sta003是SAOUHSC_00400，具有氨基酸序列SEQ ID NO：39(GI：88194195)。在Newman菌株中，其是nwmn_0401(GI：151220613)。The "sta003" antigen is annotated as "surface protein". In the NCTC 8325 strain, sta003 is SAOUHSC_00400 with the amino acid sequence of SEQ ID NO: 39 (GI: 88194195). In the Newman strain it is nwmn_0401 (GI: 151220613).

有用的sta003抗原能引发识别SEQ ID NO：39的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：39有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：39的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta003蛋白包括SEQ ID NO：39的变体。(b)的优选片段包含来自SEQ ID NO：39的表位。其它优选片段缺少SEQ ID NO：39的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：39的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：39的至少一个表位。SEQ ID NO：39的前32个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta003 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 39 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 39 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 39, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta003 proteins include variants of SEQ ID NO:39. A preferred fragment of (b) comprises an epitope from SEQ ID NO:39. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 39 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 39, While retaining at least one epitope of SEQ ID NO: 39. The first 32 N-terminal amino acids of SEQ ID NO: 39 can be usefully omitted. Other fragments omit one or more protein domains.

sta004sta004

“sta004”抗原注释为“铁载体(Siderophore)结合蛋白FatB”。在NCTC8325菌株中，sta004是SAOUHSC_00749，具有氨基酸序列SEQ ID NO：40(GI：88194514)。在Newman菌株中，其是nwmn_0705(GI：151220917)。"sta004" antigen is annotated as "siderophore (Siderophore) binding protein FatB". In the NCTC8325 strain, sta004 is SAOUHSC_00749, which has the amino acid sequence of SEQ ID NO: 40 (GI: 88194514). In the Newman strain it is nwmn_0705 (GI: 151220917).

有用的sta004抗原能引发识别SEQ ID NO：40的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：40有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：40的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta004蛋白包括SEQ ID NO：40的变体。(b)的优选片段包含来自SEQ ID NO：40的表位。其它优选片段缺少SEQ ID NO：40的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：40的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：40的至少一个表位。SEQ ID NO：40的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta004 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 40 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 40 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 40, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta004 proteins include variants of SEQ ID NO:40. A preferred fragment of (b) comprises an epitope from SEQ ID NO:40. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 40 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 40, while retaining at least one epitope of SEQ ID NO:40. The first 18 N-terminal amino acids of SEQ ID NO:40 can be usefully omitted. Other fragments omit one or more protein domains.

sta005sta005

“sta005”抗原注释为“超抗原样蛋白”。在NCTC 8325菌株中，sta005是SAOUHSC_01127，具有氨基酸序列SEQ ID NO：41(GI：88194870)。在Newman菌株中，其是nwmn_1077(GI：151221289)。The "sta005" antigen is annotated as a "superantigen-like protein". Among the NCTC 8325 strains, sta005 is SAOUHSC_01127, which has the amino acid sequence of SEQ ID NO: 41 (GI: 88194870). In the Newman strain it is nwmn_1077 (GI: 151221289).

有用的sta005抗原能引发识别SEQ ID NO：41的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：41有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：41的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta005蛋白包括SEQ ID NO：41的变体。(b)的优选片段包含来自SEQ ID NO：41的表位。其它优选片段缺少SEQ ID NO：41的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：41的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：41的至少一个表位。SEQ ID NO：41的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta005 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 41 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 41 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 41, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta005 proteins include variants of SEQ ID NO:41. A preferred fragment of (b) comprises an epitope from SEQ ID NO:41. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 41 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 41, While retaining at least one epitope of SEQ ID NO: 41. The first 18 N-terminal amino acids of SEQ ID NO: 41 can be usefully omitted. Other fragments omit one or more protein domains.

sta006sta006

“sta006”抗原注释为“铁色素(ferrichrome)-结合蛋白”，在参考文献[72]中也称为“FhuD2”。在NCTC 8325菌株中，sta006是SAOUHSC_02554，具有氨基酸序列SEQ ID NO：42(GI：88196199)。在Newman菌株中，其是nwmn_2185(GI：151222397)。The "sta006" antigen is annotated as "ferrichrome-binding protein", also referred to as "FhuD2" in ref. [72]. Among the NCTC 8325 strains, sta006 is SAOUHSC_02554 with the amino acid sequence of SEQ ID NO: 42 (GI: 88196199). In the Newman strain it is nwmn_2185 (GI: 151222397).

有用的sta006抗原能引发识别SEQ ID NO：42的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：42有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：42的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta006蛋白包括SEQ ID NO：42的变体。(b)的优选片段包含来自SEQ ID NO：42的表位。其它优选片段缺少SEQ ID NO：42的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：42的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：42的至少一个表位。SEQ ID NO：42的前17个N-末端氨基酸可有用地省去(以提供SEQ ID NO：246)。其它片段省去一个或多个蛋白质结构域。参考文献73报道了sta006的突变形式。可用，例如酰化的N-末端半胱氨酸脂化sta006抗原。一种有用的sta006序列是SEQ ID NO：248，其在N-末端具有Met-Ala-Ser-序列。Useful sta006 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 42 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 42 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 42, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta006 proteins include variants of SEQ ID NO:42. A preferred fragment of (b) comprises an epitope from SEQ ID NO:42. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 42 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 42, While retaining at least one epitope of SEQ ID NO: 42. The first 17 N-terminal amino acids of SEQ ID NO: 42 can be usefully omitted (to provide SEQ ID NO: 246). Other fragments omit one or more protein domains. Reference 73 reported a mutant form of sta006. The sta006 antigen can be lipidated with, for example, an acylated N-terminal cysteine. A useful sta006 sequence is SEQ ID NO: 248, which has a Met-Ala-Ser-sequence at the N-terminus.

sta007sta007

“sta007”抗原注释为“分泌型抗原前体”。在NCTC 8325菌株中，sta007是SAOUHSC_02571，具有氨基酸序列SEQ ID NO：43(GI：88196215)。在Newman菌株中，其是nwmn_2199(GI：151222411)。蛋白质组分析揭示该蛋白质是分泌或表面暴露的蛋白。The "sta007" antigen is annotated as "secreted antigen precursor". Among the NCTC 8325 strains, sta007 is SAOUHSC_02571 with the amino acid sequence of SEQ ID NO: 43 (GI: 88196215). In the Newman strain it is nwmn_2199 (GI: 151222411 ). Proteome analysis revealed that the protein was secreted or surface exposed.

有用的sta007抗原能引发识别SEQ ID NO：43的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：43有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：43的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta007蛋白包括SEQ ID NO：43的变体。(b)的优选片段包含来自SEQ ID NO：43的表位。其它优选片段缺少SEQ ID NO：43的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：43的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：43的至少一个表位。SEQ ID NO：43的前27个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta007 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 43 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 43 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 43, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta007 proteins include variants of SEQ ID NO:43. A preferred fragment of (b) comprises an epitope from SEQ ID NO:43. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 43 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 43, While retaining at least one epitope of SEQ ID NO:43. The first 27 N-terminal amino acids of SEQ ID NO: 43 can be usefully omitted. Other fragments omit one or more protein domains.

sta008sta008

“sta008”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta008是SAOUHSC_02650，具有氨基酸序列SEQ ID NO：44(GI：88196290)。在Newman菌株中，其是nwmn_2270(GI：151222482)。The "sta008" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta008 is SAOUHSC_02650, which has the amino acid sequence of SEQ ID NO: 44 (GI: 88196290). In the Newman strain it is nwmn_2270 (GI: 151222482).

有用的sta008抗原能引发识别SEQ ID NO：44的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：44有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：44的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta008蛋白包括SEQ ID NO：44的变体。(b)的优选片段包含来自SEQ ID NO：44的表位。其它优选片段缺少SEQ ID NO：44的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：44的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：44的至少一个表位。SEQ ID NO：44的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta008 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 44 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 44 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 44, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta008 proteins include variants of SEQ ID NO:44. A preferred fragment of (b) comprises an epitope from SEQ ID NO:44. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 44 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 44, while retaining at least one epitope of SEQ ID NO:44. The first 17 N-terminal amino acids of SEQ ID NO: 44 can be usefully omitted. Other fragments omit one or more protein domains.

sta009sta009

“sta009”抗原注释为“免疫球蛋白G-结合蛋白Sbi”。在NCTC 8325菌株中，sta009是SAOUHSC_02706，具有氨基酸序列SEQ ID NO：45(GI：88196346)。在Newman菌株中，其是nwmn_2317(GI：151222529)。The "sta009" antigen is annotated as "Immunoglobulin G-binding protein Sbi". Among the NCTC 8325 strains, sta009 is SAOUHSC_02706, which has the amino acid sequence of SEQ ID NO: 45 (GI: 88196346). In the Newman strain it is nwmn_2317 (GI: 151222529).

有用的sta009抗原能引发识别SEQ ID NO：45的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：45有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：45的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta009蛋白包括SEQ ID NO：45的变体。(b)的优选片段包含来自SEQ ID NO：45的表位。其它优选片段缺少SEQ ID NO：45的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：45的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：45的至少一个表位。SEQ ID NO：45的前29个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta009 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 45 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 45 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 45, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta009 proteins include variants of SEQ ID NO:45. A preferred fragment of (b) comprises an epitope from SEQ ID NO:45. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 45 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 45, while retaining at least one epitope of SEQ ID NO:45. The first 29 N-terminal amino acids of SEQ ID NO: 45 can be usefully omitted. Other fragments omit one or more protein domains.

sta010sta010

“sta010”抗原注释为“免疫显性抗原A”。在NCTC 8325菌株中，sta010是SAOUHSC_02887，具有氨基酸序列SEQ ID NO：46(GI：88196515)。在Newman菌株中，其是nwmn_2469(GI：151222681)。蛋白质组分析揭示该蛋白质是分泌或表面暴露的蛋白。The "sta010" antigen was annotated as "immunodominant antigen A". In NCTC 8325 strain, sta010 is SAOUHSC_02887 with amino acid sequence SEQ ID NO: 46 (GI: 88196515). In the Newman strain it is nwmn_2469 (GI: 151222681 ). Proteome analysis revealed that the protein was secreted or surface exposed.

有用的sta010抗原能引发识别SEQ ID NO：46的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：46有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：46的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta010蛋白包括SEQ ID NO：46的变体。(b)的优选片段包含来自SEQ ID NO：46的表位。其它优选片段缺少SEQ ID NO：46的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：46的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：46的至少一个表位。SEQ ID NO：46的前29个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta010 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 46 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 46 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 46, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta010 proteins include variants of SEQ ID NO:46. A preferred fragment of (b) comprises an epitope from SEQ ID NO:46. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 46 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 46, While retaining at least one epitope of SEQ ID NO:46. The first 29 N-terminal amino acids of SEQ ID NO: 46 can be usefully omitted. Other fragments omit one or more protein domains.

sta011sta011

“sta011”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta011是SAOUHSC_00052，具有氨基酸序列SEQ ID NO：47(GI：88193872)。The "sta011" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta011 is SAOUHSC_00052, which has the amino acid sequence of SEQ ID NO: 47 (GI: 88193872).

有用的sta011抗原能引发识别SEQ ID NO：47的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：47有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：47的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta011蛋白包括SEQ ID NO：47的变体。(b)的优选片段包含来自SEQ ID NO：47的表位。其它优选片段缺少SEQ ID NO：47的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：47的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：47的至少一个表位。SEQ ID NO：47的前23个N-末端氨基酸可有用地省去(以提供SEQ ID NO：247)。其它片段省去一个或多个蛋白质结构域。可用，例如酰化的N-末端半胱氨酸脂化sta011抗原。一种有用的sta011序列是SEQ ID NO：249，其具有N-末端甲硫氨酸。Useful sta011 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 47 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 47 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 47, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta011 proteins include variants of SEQ ID NO:47. A preferred fragment of (b) comprises an epitope from SEQ ID NO:47. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 47 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 47, while retaining at least one epitope of SEQ ID NO:47. The first 23 N-terminal amino acids of SEQ ID NO: 47 can be usefully omitted (to provide SEQ ID NO: 247). Other fragments omit one or more protein domains. The staO11 antigen can be lipidated with, for example, an acylated N-terminal cysteine. A useful sta011 sequence is SEQ ID NO: 249, which has an N-terminal methionine.

可用作sta011抗原或制备sta011抗原的各种形式SEQ ID NO：47包括但不限于含各种Ile/Val/Leu取代的SEQ ID NO：213、214和215。Various forms of SEQ ID NO: 47 that can be used as or to prepare sta011 antigens include, but are not limited to, SEQ ID NOs: 213, 214 and 215 with various Ile/Val/Leu substitutions.

Sta011可存在单体或寡聚物，Ca++离子有利于寡聚。本发明可利用Sta011的单体和/或寡聚物。Sta011 can exist as monomer or oligomer, and Ca ++ ion favors oligomerization. Monomers and/or oligomers of Sta011 may be utilized in the present invention.

sta012sta012

“sta012”抗原注释为“含前导序列的蛋白”。在NCTC 8325菌株中，sta012是SAOUHSC_00106，具有氨基酸序列SEQ ID NO：48(GI：88193919)。The "sta012" antigen is annotated as "leader-containing protein". In the NCTC 8325 strain, sta012 is SAOUHSC_00106, which has the amino acid sequence of SEQ ID NO: 48 (GI: 88193919).

有用的sta012抗原能引发识别SEQ ID NO：48的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：48有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：48的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta012蛋白包括SEQ ID NO：48的变体。(b)的优选片段包含来自SEQ ID NO：48的表位。其它优选片段缺少SEQ ID NO：48的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：48的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：48的至少一个表位。SEQ ID NO：48的前21个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta012 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 48 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 48 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 48, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta012 proteins include variants of SEQ ID NO:48. A preferred fragment of (b) comprises an epitope from SEQ ID NO:48. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 48 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 48, While retaining at least one epitope of SEQ ID NO:48. The first 21 N-terminal amino acids of SEQ ID NO: 48 can be usefully omitted. Other fragments omit one or more protein domains.

sta013sta013

“sta013”抗原注释为“多聚-γ-谷氨酸被膜生物合成蛋白”。在NCTC8325菌株中，sta013是SAOUHSC_00107，具有氨基酸序列SEQ ID NO：49(GI：88193920)。The "sta013" antigen is annotated as "poly-γ-glutamate envelope biosynthesis protein". In the NCTC8325 strain, sta013 is SAOUHSC_00107, which has the amino acid sequence of SEQ ID NO: 49 (GI: 88193920).

有用的sta013抗原能引发识别SEQ ID NO：49的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：49有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：49的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta013蛋白包括SEQ ID NO：49的变体。(b)的优选片段包含来自SEQ ID NO：49的表位。其它优选片段缺少SEQ ID NO：49的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：49的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：49的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta013 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 49 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 49 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 49, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta013 proteins include variants of SEQ ID NO:49. A preferred fragment of (b) comprises an epitope from SEQ ID NO:49. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 49 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 49, While retaining at least one epitope of SEQ ID NO:49. Other fragments omit one or more protein domains.

sta014sta014

“sta014”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta014是SAOUHSC_00137，具有氨基酸序列SEQ ID NO：50(GI：88193950)。The "sta014" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta014 is SAOUHSC_00137, which has the amino acid sequence of SEQ ID NO: 50 (GI: 88193950).

有用的sta014抗原能引发识别SEQ ID NO：50的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：50有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：50的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta014蛋白包括SEQ ID NO：50的变体。(b)的优选片段包含来自SEQ ID NO：50的表位。其它优选片段缺少SEQ ID NO：50的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：50的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：50的至少一个表位。SEQ ID NO：50的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta014 antigens are capable of eliciting antibodies that recognize SEQ ID NO:50 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:50 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 50, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta014 proteins include variants of SEQ ID NO:50. A preferred fragment of (b) comprises an epitope from SEQ ID NO:50. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 50 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 50, while retaining at least one epitope of SEQ ID NO:50. The first 17 N-terminal amino acids of SEQ ID NO:50 can be usefully omitted. Other fragments omit one or more protein domains.

sta015sta015

“sta015”抗原注释为“胞外溶质-结合蛋白；含RGD的脂蛋白”。在NCTC 8325菌株中，sta015是SAOUHSC_00170，具有氨基酸序列SEQ IDNO：51(GI：88193980)。The "sta015" antigen is annotated as "Exosol-binding protein; RGD-containing lipoprotein". In the NCTC 8325 strain, sta015 is SAOUHSC_00170, which has the amino acid sequence of SEQ ID NO: 51 (GI: 88193980).

有用的sta015抗原能引发识别SEQ ID NO：51的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：51有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：51的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta015蛋白包括SEQ ID NO：51的变体。(b)的优选片段包含来自SEQ ID NO：51的表位。其它优选片段缺少SEQ ID NO：51的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：51的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：51的至少一个表位。SEQ ID NO：51的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta015 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 51 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 51 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 51, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta015 proteins include variants of SEQ ID NO:51. A preferred fragment of (b) comprises an epitope from SEQ ID NO:51. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 51 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 51, while retaining at least one epitope of SEQ ID NO:51. The first 18 N-terminal amino acids of SEQ ID NO: 51 can be usefully omitted. Other fragments omit one or more protein domains.

sta016sta016

“sta016”抗原注释为“γ-谷氨酰转肽酶”。在NCTC 8325菌株中，sta016是SAOUHSC_00171，具有氨基酸序列SEQ ID NO：52(GI：88193981)。The "sta016" antigen is annotated as "γ-glutamyl transpeptidase". In the NCTC 8325 strain, sta016 is SAOUHSC_00171, which has the amino acid sequence of SEQ ID NO: 52 (GI: 88193981).

有用的sta016抗原能引发识别SEQ ID NO：52的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：52有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：52的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta016蛋白包括SEQ ID NO：52的变体。(b)的优选片段包含来自SEQ ID NO：52的表位。其它优选片段缺少SEQ ID NO：52的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：52的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：52的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta016 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 52 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 52 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:52, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta016 proteins include variants of SEQ ID NO:52. A preferred fragment of (b) comprises an epitope from SEQ ID NO:52. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 52 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 52, while retaining at least one epitope of SEQ ID NO:52. Other fragments omit one or more protein domains.

sta017sta017

“sta017”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta017是SAOUHSC_00186，具有氨基酸序列SEQ ID NO：53(GI：88193996)。The "sta017" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta017 is SAOUHSC_00186, which has the amino acid sequence of SEQ ID NO: 53 (GI: 88193996).

有用的sta017抗原能引发识别SEQ ID NO：53的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：53有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：53的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta017蛋白包括SEQ ID NO：53的变体。(b)的优选片段包含来自SEQ ID NO：53的表位。其它优选片段缺少SEQ ID NO：53的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：53的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：53的至少一个表位。SEQ ID NO：53的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta017 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 53 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 53 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 53, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta017 proteins include variants of SEQ ID NO:53. A preferred fragment of (b) comprises an epitope from SEQ ID NO:53. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 53 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 53, While retaining at least one epitope of SEQ ID NO:53. The first 17 N-terminal amino acids of SEQ ID NO:53 can be usefully omitted. Other fragments omit one or more protein domains.

sta018sta018

“sta018”抗原注释为“胞外溶质-结合蛋白”。在NCTC 8325菌株中，sta018是SAOUHSC_00201，具有氨基酸序列SEQ ID NO：54(GI：88194011)。The "sta018" antigen is annotated as "exosol-binding protein". In the NCTC 8325 strain, sta018 is SAOUHSC_00201, which has the amino acid sequence of SEQ ID NO: 54 (GI: 88194011).

有用的sta018抗原能引发识别SEQ ID NO：54的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：54有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：54的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta018蛋白包括SEQ ID NO：54的变体。(b)的优选片段包含来自SEQ ID NO：54的表位。其它优选片段缺少SEQ ID NO：54的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：54的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：54的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta018 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 54 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 54 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 54, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta018 proteins include variants of SEQ ID NO:54. A preferred fragment of (b) comprises an epitope from SEQ ID NO:54. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 54 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 54, while retaining at least one epitope of SEQ ID NO:54. Other fragments omit one or more protein domains.

sta019sta019

“sta019”抗原注释为“肽聚糖水解酶”。在NCTC 8325菌株中，sta019是SAOUHSC_00248，具有氨基酸序列SEQ ID NO：55(GI：88194055)。在Newman菌株中，其是nwmn_0210(GI：151220422)。The "sta019" antigen is annotated as "peptidoglycan hydrolase". In the NCTC 8325 strain, sta019 is SAOUHSC_00248, which has the amino acid sequence of SEQ ID NO: 55 (GI: 88194055). In the Newman strain it is nwmn_0210 (GI: 151220422).

有用的sta019抗原能引发识别SEQ ID NO：55的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：55有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：55的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta019蛋白包括SEQ ID NO：55的变体。(b)的优选片段包含来自SEQ ID NO：55的表位。其它优选片段缺少SEQ ID NO：55的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：55的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：55的至少一个表位。SEQ ID NO：55的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。有用的片段是SEQ ID NO：228和229。Useful sta019 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 55 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 55 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 55, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta019 proteins include variants of SEQ ID NO:55. A preferred fragment of (b) comprises an epitope from SEQ ID NO:55. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 55 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 55, while retaining at least one epitope of SEQ ID NO:55. The first 25 N-terminal amino acids of SEQ ID NO:55 can be usefully omitted. Other fragments omit one or more protein domains. Useful fragments are SEQ ID NO: 228 and 229.

Sta019不能很好地吸附于氢氧化铝佐剂，因此，组合物中存在的Sta019可以是未吸附的或可吸附于其它佐剂，例如磷酸铝。StaO19 does not adsorb well to aluminum hydroxide adjuvants, therefore, StaO19 present in the composition may be unadsorbed or adsorbable to other adjuvants, such as aluminum phosphate.

sta020sta020

“sta020”抗原注释为“输出蛋白”。在NCTC 8325菌株中，sta020是SAOUHSC_00253，具有氨基酸序列SEQ ID NO：56(GI：88194059)。The "sta020" antigen is annotated as "export protein". In NCTC 8325 strain, sta020 is SAOUHSC_00253 with amino acid sequence SEQ ID NO: 56 (GI: 88194059).

有用的sta020抗原能引发识别SEQ ID NO：56的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：56有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：56的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta020蛋白包括SEQ ID NO：56的变体。(b)的优选片段包含来自SEQ ID NO：56的表位。其它优选片段缺少SEQ ID NO：56的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：56的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：56的至少一个表位。SEQ ID NO：56的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta020 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 56 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 56 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 56, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta020 proteins include variants of SEQ ID NO:56. A preferred fragment of (b) comprises an epitope from SEQ ID NO:56. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 56 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 56, While retaining at least one epitope of SEQ ID NO:56. The first 30 N-terminal amino acids of SEQ ID NO: 56 can be usefully omitted. Other fragments omit one or more protein domains.

sta021sta021

“sta021”抗原注释为“分泌型抗原SsaA-样蛋白”。在NCTC 8325菌株中，sta021是SAOUHSC_00256，具有氨基酸序列SEQ ID NO：57(GI：88194062)。The "sta021" antigen is annotated as "secreted antigen SsaA-like protein". In the NCTC 8325 strain, sta021 is SAOUHSC_00256, which has the amino acid sequence of SEQ ID NO: 57 (GI: 88194062).

有用的sta021抗原能引发识别SEQ ID NO：57的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：57有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：57的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta021蛋白包括SEQ ID NO：57的变体。(b)的优选片段包含来自SEQ ID NO：57的表位。其它优选片段缺少SEQ ID NO：57的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：57的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：57的至少一个表位。SEQ ID NO：57的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta021 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 57 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 57 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 57, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta021 proteins include variants of SEQ ID NO:57. A preferred fragment of (b) comprises an epitope from SEQ ID NO:57. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 57 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 57, while retaining at least one epitope of SEQ ID NO:57. The first 24 N-terminal amino acids of SEQ ID NO: 57 can be usefully omitted. Other fragments omit one or more protein domains.

sta022sta022

“sta022”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta022是SAOUHSC_00279，具有氨基酸序列SEQ ID NO：58(GI：88194083)。The "sta022" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta022 is SAOUHSC_00279, which has the amino acid sequence of SEQ ID NO: 58 (GI: 88194083).

有用的sta022抗原能引发识别SEQ ID NO：58的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：58有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：58的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta022蛋白包括SEQ ID NO：58的变体。(b)的优选片段包含来自SEQ ID NO：58的表位。其它优选片段缺少SEQ ID NO：58的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：58的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：58的至少一个表位。SEQ ID NO：58的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta022 antigens can elicit antibodies that recognize SEQ ID NO: 58 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 58 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 58, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta022 proteins include variants of SEQ ID NO:58. A preferred fragment of (b) comprises an epitope from SEQ ID NO:58. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 58 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 58, While retaining at least one epitope of SEQ ID NO:58. The first 17 N-terminal amino acids of SEQ ID NO:58 can be usefully omitted. Other fragments omit one or more protein domains.

sta023sta023

“sta023”抗原注释为“5-核苷酸酶；脂多糖e(P4)家族”。在NCTC 8325菌株中，sta023是SAOUHSC_00284，具有氨基酸序列SEQ ID NO：59(GI：88194087)。The "sta023" antigen is annotated as "5-nucleotidase; lipopolysaccharide e(P4) family". In the NCTC 8325 strain, sta023 is SAOUHSC_00284, which has the amino acid sequence of SEQ ID NO: 59 (GI: 88194087).

有用的sta023抗原能引发识别SEQ ID NO：59的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：59有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：59的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta023蛋白包括SEQ ID NO：59的变体。(b)的优选片段包含来自SEQ ID NO：59的表位。其它优选片段缺少SEQ ID NO：59的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：59的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：59的至少一个表位。SEQ ID NO：59的前31个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta023 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 59 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 59 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 59, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta023 proteins include variants of SEQ ID NO:59. A preferred fragment of (b) comprises an epitope from SEQ ID NO:59. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 59 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 59, While retaining at least one epitope of SEQ ID NO:59. The first 31 N-terminal amino acids of SEQ ID NO: 59 can be usefully omitted. Other fragments omit one or more protein domains.

sta024sta024

“sta024”抗原注释为“脂酶前体”。在NCTC 8325菌株中，sta024是SAOUHSC_00300，具有氨基酸序列SEQ ID NO：60(GI：88194101)。The "sta024" antigen is annotated as "lipase precursor". In the NCTC 8325 strain, sta024 is SAOUHSC_00300, having the amino acid sequence of SEQ ID NO: 60 (GI: 88194101).

有用的sta024抗原能引发识别SEQ ID NO：60的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：60有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：60的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta024蛋白包括SEQ ID NO：60的变体。(b)的优选片段包含来自SEQ ID NO：60的表位。其它优选片段缺少SEQ ID NO：60的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：60的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：60的至少一个表位。SEQ ID NO：60的前37个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta024 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 60 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 60 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:60, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta024 proteins include variants of SEQ ID NO:60. A preferred fragment of (b) comprises an epitope from SEQ ID NO:60. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 60 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 60, While retaining at least one epitope of SEQ ID NO:60. The first 37 N-terminal amino acids of SEQ ID NO:60 can be usefully omitted. Other fragments omit one or more protein domains.

sta025sta025

“sta025”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta025是SAOUHSC_00362，具有氨基酸序列SEQ ID NO：61(GI：88194160)。The "sta025" antigen is annotated as "lipoprotein". Among the NCTC 8325 strains, sta025 is SAOUHSC_00362, which has the amino acid sequence of SEQ ID NO: 61 (GI: 88194160).

有用的sta025抗原能引发识别SEQ ID NO：61的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：61有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：61的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta025蛋白包括SEQ ID NO：61的变体。(b)的优选片段包含来自SEQ ID NO：61的表位。其它优选片段缺少SEQ ID NO：61的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：61的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：61的至少一个表位。SEQ ID NO：61的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta025 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 61 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 61 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 61, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta025 proteins include variants of SEQ ID NO:61. A preferred fragment of (b) comprises an epitope from SEQ ID NO:61. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 61 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 61, While retaining at least one epitope of SEQ ID NO:61. The first 19 N-terminal amino acids of SEQ ID NO:61 can be usefully omitted. Other fragments omit one or more protein domains.

sta026sta026

“sta026”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta026是SAOUHSC_00404，具有氨基酸序列SEQ ID NO：62(GI：88194198)。The "sta026" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta026 is SAOUHSC_00404, which has the amino acid sequence of SEQ ID NO: 62 (GI: 88194198).

有用的sta026抗原能引发识别SEQ ID NO：62的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：62有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：62的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta026蛋白包括SEQ ID NO：62的变体。(b)的优选片段包含来自SEQ ID NO：62的表位。其它优选片段缺少SEQ ID NO：62的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：62的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：62的至少一个表位。SEQ ID NO：62的前22个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta026 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 62 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 62 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 62, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta026 proteins include variants of SEQ ID NO:62. A preferred fragment of (b) comprises an epitope from SEQ ID NO:62. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 62 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 62, While retaining at least one epitope of SEQ ID NO:62. The first 22 N-terminal amino acids of SEQ ID NO:62 can be usefully omitted. Other fragments omit one or more protein domains.

sta027sta027

“sta027”抗原注释为“可能的脂酶”。在NCTC 8325菌株中，sta027是SAOUHSC_00661，具有氨基酸序列SEQ ID NO：63(GI：88194426)。The "sta027" antigen was annotated as "possible lipase". In the NCTC 8325 strain, sta027 is SAOUHSC_00661, which has the amino acid sequence of SEQ ID NO: 63 (GI: 88194426).

有用的sta027抗原能引发识别SEQ ID NO：63的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：63有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：63的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta027蛋白包括SEQ ID NO：63的变体。(b)的优选片段包含来自SEQ ID NO：63的表位。其它优选片段缺少SEQ ID NO：63的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：63的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：63的至少一个表位。SEQ ID NO：63的前23个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta027 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 63 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 63 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:63, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta027 proteins include variants of SEQ ID NO:63. A preferred fragment of (b) comprises an epitope from SEQ ID NO:63. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 63 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 63, While retaining at least one epitope of SEQ ID NO:63. The first 23 N-terminal amino acids of SEQ ID NO:63 can be usefully omitted. Other fragments omit one or more protein domains.

sta028sta028

“sta028”抗原注释为“分泌型抗原SsaA-样蛋白”。在NCTC 8325菌株中，sta028是SAOUHSC_00671，具有氨基酸序列SEQ ID NO：64(GI：88194436)。在Newman菌株中，其是nwmn_0634(GI：151220846)。The "sta028" antigen is annotated as "secreted antigen SsaA-like protein". In NCTC 8325 strain, sta028 is SAOUHSC_00671 with amino acid sequence SEQ ID NO: 64 (GI: 88194436). In the Newman strain it is nwmn_0634 (GI: 151220846).

有用的sta028抗原能引发识别SEQ ID NO：64的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：64有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：64的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta028蛋白包括SEQ ID NO：64的变体。(b)的优选片段包含来自SEQ ID NO：64的表位。其它优选片段缺少SEQ ID NO：64的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：64的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：64的至少一个表位。SEQ ID NO：64的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta028 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 64 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 64 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:64, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta028 proteins include variants of SEQ ID NO:64. A preferred fragment of (b) comprises an epitope from SEQ ID NO:64. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 64 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 64, While retaining at least one epitope of SEQ ID NO:64. The first 25 N-terminal amino acids of SEQ ID NO:64 can be usefully omitted. Other fragments omit one or more protein domains.

sta029sta029

“sta029”抗原注释为“铁色素结合蛋白”。在NCTC 8325菌株中，sta029是SAOUHSC_00754，具有氨基酸序列SEQ ID NO：65(GI：88194518)。The "sta029" antigen is annotated as "ferrochrome-binding protein". In the NCTC 8325 strain, sta029 is SAOUHSC_00754, which has the amino acid sequence of SEQ ID NO: 65 (GI: 88194518).

有用的sta029抗原能引发识别SEQ ID NO：65的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：65有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：65的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta029蛋白包括SEQ ID NO：65的变体。(b)的优选片段包含来自SEQ ID NO：65的表位。其它优选片段缺少SEQ ID NO：65的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：65的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：65的至少一个表位。SEQ ID NO：65的最后25个C-末端氨基酸可有用地省去。SEQ ID NO：65的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta029 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 65 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 65 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 65, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta029 proteins include variants of SEQ ID NO:65. A preferred fragment of (b) comprises an epitope from SEQ ID NO:65. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 65 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 65, While retaining at least one epitope of SEQ ID NO:65. The last 25 C-terminal amino acids of SEQ ID NO:65 can be usefully omitted. The first 19 N-terminal amino acids of SEQ ID NO:65 can be usefully omitted. Other fragments omit one or more protein domains.

sta030sta030

“sta030”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta030是SAOUHSC_00808，具有氨基酸序列SEQ ID NO：66(GI：88194568)。The "sta030" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta030 is SAOUHSC_00808, which has the amino acid sequence of SEQ ID NO: 66 (GI: 88194568).

有用的sta030抗原能引发识别SEQ ID NO：66的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：66有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：66的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta030蛋白包括SEQ ID NO：66的变体。(b)的优选片段包含来自SEQ ID NO：66的表位。其它优选片段缺少SEQ ID NO：66的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：66的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：66的至少一个表位。SEQ ID NO：66的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta030 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 66 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 66 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 66, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta030 proteins include variants of SEQ ID NO:66. A preferred fragment of (b) comprises an epitope from SEQ ID NO:66. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 66 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 66, While retaining at least one epitope of SEQ ID NO:66. The first 17 N-terminal amino acids of SEQ ID NO:66 can be usefully omitted. Other fragments omit one or more protein domains.

sta031sta031

“sta031”抗原注释为“5-核苷酸酶家族蛋白”。在NCTC 8325菌株中，sta031是SAOUHSC_00860，具有氨基酸序列SEQ ID NO：67(GI：88194617)。The "sta031" antigen is annotated as "5-nucleotidase family protein". In the NCTC 8325 strain, sta031 is SAOUHSC_00860, which has the amino acid sequence of SEQ ID NO: 67 (GI: 88194617).

有用的sta031抗原能引发识别SEQ ID NO：67的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：67有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：67的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta031蛋白包括SEQ ID NO：67的变体。(b)的优选片段包含来自SEQ ID NO：67的表位。其它优选片段缺少SEQ ID NO：67的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：67的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：67的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta031 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 67 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 67 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 67, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta031 proteins include variants of SEQ ID NO:67. A preferred fragment of (b) comprises an epitope from SEQ ID NO:67. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 67 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 67, While retaining at least one epitope of SEQ ID NO:67. Other fragments omit one or more protein domains.

sta032sta032

“sta032”抗原注释为“丝氨酸蛋白酶HtrA”。在NCTC 8325菌株中，sta032是SAOUHSC_00958，具有氨基酸序列SEQ ID NO：68(GI：88194715)。The "sta032" antigen is annotated as "serine protease HtrA". In the NCTC 8325 strain, sta032 is SAOUHSC_00958, which has the amino acid sequence of SEQ ID NO: 68 (GI: 88194715).

有用的sta032抗原能引发识别SEQ ID NO：68的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：68有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：68的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta032蛋白包括SEQ ID NO：68的变体。(b)的优选片段包含来自SEQ ID NO：68的表位。其它优选片段缺少SEQ ID NO：68的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：68的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：68的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta032 antigens can elicit antibodies that recognize SEQ ID NO: 68 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 68 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 68, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta032 proteins include variants of SEQ ID NO:68. A preferred fragment of (b) comprises an epitope from SEQ ID NO:68. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 68 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 68, While retaining at least one epitope of SEQ ID NO:68. Other fragments omit one or more protein domains.

sta033sta033

“sta033”抗原注释为“丝氨酸蛋白酶前体”。在NCTC 8325菌株中，sta033是SAOUHSC_00987，具有氨基酸序列SEQ ID NO：69(GI：88194744)。The "sta033" antigen is annotated as "precursor serine protease". In NCTC 8325 strain, sta033 is SAOUHSC_00987 with amino acid sequence SEQ ID NO: 69 (GI: 88194744).

有用的sta033抗原能引发识别SEQ ID NO：69的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：69有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：69的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta033蛋白包括SEQ ID NO：69的变体。(b)的优选片段包含来自SEQ ID NO：69的表位。其它优选片段缺少SEQ ID NO：69的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：69的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：69的至少一个表位。SEQ ID NO：69的前29个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta033 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 69 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 69 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 69, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta033 proteins include variants of SEQ ID NO:69. A preferred fragment of (b) comprises an epitope from SEQ ID NO:69. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 69 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 69, While retaining at least one epitope of SEQ ID NO:69. The first 29 N-terminal amino acids of SEQ ID NO:69 can be usefully omitted. Other fragments omit one or more protein domains.

sta034sta034

“sta034”抗原注释为“谷氨酰内肽酶前体”。在NCTC 8325菌株中，sta034是SAOUHSC_00988，具有氨基酸序列SEQ ID NO：70(GI：88194745)。The "sta034" antigen is annotated as "glutamyl endopeptidase precursor". In the NCTC 8325 strain, sta034 is SAOUHSC_00988, which has the amino acid sequence of SEQ ID NO: 70 (GI: 88194745).

有用的sta034抗原能引发识别SEQ ID NO：70的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：70有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：70的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta034蛋白包括SEQ ID NO：70的变体。(b)的优选片段包含来自SEQ ID NO：70的表位。其它优选片段缺少SEQ ID NO：70的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：70的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：70的至少一个表位。SEQ ID NO：70的前29个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta034 antigens are capable of eliciting antibodies that recognize SEQ ID NO:70 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:70 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:70, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta034 proteins include variants of SEQ ID NO:70. A preferred fragment of (b) comprises an epitope from SEQ ID NO:70. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 70 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 70, while retaining at least one epitope of SEQ ID NO:70. The first 29 N-terminal amino acids of SEQ ID NO:70 can be usefully omitted. Other fragments omit one or more protein domains.

sta035sta035

“sta035”抗原注释为“fmt蛋白”。在NCTC 8325菌株中，sta035是SAOUHSC_00998，具有氨基酸序列SEQ ID NO：71(GI：88194754)。The "sta035" antigen is annotated as "fmt protein". In the NCTC 8325 strain, sta035 is SAOUHSC_00998, which has the amino acid sequence of SEQ ID NO: 71 (GI: 88194754).

有用的sta035抗原能引发识别SEQ ID NO：71的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：71有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：71的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta035蛋白包括SEQ ID NO：71的变体。(b)的优选片段包含来自SEQ ID NO：71的表位。其它优选片段缺少SEQ ID NO：71的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：71的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：71的至少一个表位。SEQ ID NO：71的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta035 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 71 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 71 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 71, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta035 proteins include variants of SEQ ID NO:71. A preferred fragment of (b) comprises an epitope from SEQ ID NO:71. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 71 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 71, While retaining at least one epitope of SEQ ID NO:71. The first 25 N-terminal amino acids of SEQ ID NO: 71 can be usefully omitted. Other fragments omit one or more protein domains.

sta036sta036

“sta036”抗原注释为“含前导序列的铁-调节蛋白”。在NCTC 8325菌株中，sta036是SAOUHSC_01084，具有氨基酸序列SEQ ID NO：72(GI：88194831)。The "sta036" antigen is annotated as "iron-regulatory protein with leader sequence". In NCTC 8325 strain, sta036 is SAOUHSC_01084 with amino acid sequence SEQ ID NO: 72 (GI: 88194831).

有用的sta036抗原能引发识别SEQ ID NO：72的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：72有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：72的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta036蛋白包括SEQ ID NO：72的变体。(b)的优选片段包含来自SEQ ID NO：72的表位。其它优选片段缺少SEQ ID NO：72的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：72的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：72的至少一个表位。SEQ ID NO：72的最后27个N-末端氨基酸可有用地省去。SEQ ID NO：72的前32个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta036 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 72 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 72 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 72, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta036 proteins include variants of SEQ ID NO:72. A preferred fragment of (b) comprises an epitope from SEQ ID NO:72. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 72 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 72, While retaining at least one epitope of SEQ ID NO:72. The last 27 N-terminal amino acids of SEQ ID NO:72 can be usefully omitted. The first 32 N-terminal amino acids of SEQ ID NO:72 can be usefully omitted. Other fragments omit one or more protein domains.

sta037sta037

“sta037”抗原注释为“铁ABC转运蛋白；铁-结合蛋白IsdE”。在NCTC 8325菌株中，sta037是SAOUHSC_01085，具有氨基酸序列SEQ IDNO：73(GI：88194832)。The "sta037" antigen is annotated as "Iron ABC transporter; Iron-binding protein IsdE". In the NCTC 8325 strain, sta037 is SAOUHSC_01085, having the amino acid sequence of SEQ ID NO: 73 (GI: 88194832).

有用的sta037抗原能引发识别SEQ ID NO：73的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：73有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：73的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta037蛋白包括SEQ ID NO：73的变体。(b)的优选片段包含来自SEQ ID NO：73的表位。其它优选片段缺少SEQ ID NO：73的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：73的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：73的至少一个表位。SEQ ID NO：73的前9个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta037 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 73 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 73 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:73, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta037 proteins include variants of SEQ ID NO:73. A preferred fragment of (b) comprises an epitope from SEQ ID NO:73. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 73 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 73, While retaining at least one epitope of SEQ ID NO:73. The first 9 N-terminal amino acids of SEQ ID NO:73 can be usefully omitted. Other fragments omit one or more protein domains.

sta038sta038

“sta038”抗原注释为“NPQTN特异性分选酶B”。在NCTC 8325菌株中，sta038是SAOUHSC_01088，具有氨基酸序列SEQ ID NO：74(GI：88194835)。The "sta038" antigen is annotated as "NPQTN-specific sortase B". In the NCTC 8325 strain, sta038 is SAOUHSC_01088, which has the amino acid sequence of SEQ ID NO: 74 (GI: 88194835).

有用的sta038抗原能引发识别SEQ ID NO：74的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：74有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：74的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta038蛋白包括SEQ ID NO：74的变体。(b)的优选片段包含来自SEQ ID NO：74的表位。其它优选片段缺少SEQ ID NO：74的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：74的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：74的至少一个表位。SEQ ID NO：74的前21个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta038 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 74 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 74 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 74, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta038 proteins include variants of SEQ ID NO:74. A preferred fragment of (b) comprises an epitope from SEQ ID NO:74. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 74 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 74, While retaining at least one epitope of SEQ ID NO:74. The first 21 N-terminal amino acids of SEQ ID NO:74 can be usefully omitted. Other fragments omit one or more protein domains.

sta039sta039

“sta039”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta039是SAOUHSC_01124，具有氨基酸序列SEQ ID NO：75(GI：88194868)。The "sta039" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta039 is SAOUHSC_01124, which has the amino acid sequence of SEQ ID NO: 75 (GI: 88194868).

有用的sta039抗原能引发识别SEQ ID NO：75的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：75有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：75的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta039蛋白包括SEQ ID NO：75的变体。(b)的优选片段包含来自SEQ ID NO：75的表位。其它优选片段缺少SEQ ID NO：75的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：75的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：75的至少一个表位。SEQ ID NO：75的前22个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta039 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 75 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 75 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 75, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta039 proteins include variants of SEQ ID NO:75. A preferred fragment of (b) comprises an epitope from SEQ ID NO:75. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 75 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 75, while retaining at least one epitope of SEQ ID NO:75. The first 22 N-terminal amino acids of SEQ ID NO: 75 can be usefully omitted. Other fragments omit one or more protein domains.

sta040sta040

“sta040”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta040是SAOUHSC_01125，具有氨基酸序列SEQ ID NO：76(GI：88194869)。在Newman菌株中，其是nwmn_1076(GI：151221288)。The "sta040" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta040 is SAOUHSC_01125, which has the amino acid sequence of SEQ ID NO: 76 (GI: 88194869). In the Newman strain it is nwmn_1076 (GI: 151221288).

有用的sta040抗原能引发识别SEQ ID NO：76的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：76有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：76的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta040蛋白包括SEQ ID NO：76的变体。(b)的优选片段包含来自SEQ ID NO：76的表位。其它优选片段缺少SEQ ID NO：76的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：76的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：76的至少一个表位。SEQ ID NO：76的前21个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta040 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 76 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 76 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 76, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta040 proteins include variants of SEQ ID NO:76. A preferred fragment of (b) comprises an epitope from SEQ ID NO:76. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 76 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 76, While retaining at least one epitope of SEQ ID NO:76. The first 21 N-terminal amino acids of SEQ ID NO: 76 can be usefully omitted. Other fragments omit one or more protein domains.

sta041sta041

“sta041”抗原注释为“相关的纤连蛋白-结合蛋白A”。在NCTC 8325菌株中，sta041是SAOUHSC_01175，具有氨基酸序列SEQ ID NO：77(GI：88194914)。The "sta041" antigen is annotated as "related fibronectin-binding protein A". Among the NCTC 8325 strains, sta041 is SAOUHSC_01175, which has the amino acid sequence of SEQ ID NO: 77 (GI: 88194914).

有用的sta041抗原能引发识别SEQ ID NO：77的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：77有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：77的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta041蛋白包括SEQ ID NO：77的变体。(b)的优选片段包含来自SEQ ID NO：77的表位。其它优选片段缺少SEQ ID NO：77的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：77的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：77的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta041 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 77 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 77 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 77, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta041 proteins include variants of SEQ ID NO:77. A preferred fragment of (b) comprises an epitope from SEQ ID NO:77. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 77 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 77, while retaining at least one epitope of SEQ ID NO:77. Other fragments omit one or more protein domains.

sta042sta042

“sta042”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta042是SAOUHSC_01180，具有氨基酸序列SEQ ID NO：78(GI：88194919)。The "sta042" antigen is annotated as "lipoprotein". In NCTC 8325 strain, sta042 is SAOUHSC_01180 with amino acid sequence SEQ ID NO: 78 (GI: 88194919).

有用的sta042抗原能引发识别SEQ ID NO：78的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：78有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：78的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta042蛋白包括SEQ ID NO：78的变体。(b)的优选片段包含来自SEQ ID NO：78的表位。其它优选片段缺少SEQ ID NO：78的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：78的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：78的至少一个表位。SEQ ID NO：78的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta042 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 78 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 78 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 78, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta042 proteins include variants of SEQ ID NO:78. A preferred fragment of (b) comprises an epitope from SEQ ID NO:78. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 78 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 78, While retaining at least one epitope of SEQ ID NO:78. The first 18 N-terminal amino acids of SEQ ID NO: 78 can be usefully omitted. Other fragments omit one or more protein domains.

sta043sta043

“sta043”抗原注释为“细胞壁水解酶”。在NCTC 8325菌株中，sta043是SAOUHSC_01219，具有氨基酸序列SEQ ID NO：79(GI：88194955)。The "sta043" antigen is annotated as "cell wall hydrolase". In the NCTC 8325 strain, sta043 is SAOUHSC_01219, which has the amino acid sequence of SEQ ID NO: 79 (GI: 88194955).

有用的sta043抗原能引发识别SEQ ID NO：79的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：79有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：79的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta043蛋白包括SEQ ID NO：79的变体。(b)的优选片段包含来自SEQ ID NO：79的表位。其它优选片段缺少SEQ ID NO：79的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：79的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：79的至少一个表位。SEQ ID NO：79的前38个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta043 antigens can elicit antibodies that recognize SEQ ID NO: 79 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 79 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 79, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta043 proteins include variants of SEQ ID NO:79. A preferred fragment of (b) comprises an epitope from SEQ ID NO:79. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 79 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 79, While retaining at least one epitope of SEQ ID NO:79. The first 38 N-terminal amino acids of SEQ ID NO: 79 can be usefully omitted. Other fragments omit one or more protein domains.

sta044sta044

“sta044”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta044是SAOUHSC_01508，具有氨基酸序列SEQ ID NO：80(GI：88195223)。The "sta044" antigen is annotated as "lipoprotein". In NCTC 8325 strain, sta044 is SAOUHSC_01508 with amino acid sequence SEQ ID NO: 80 (GI: 88195223).

有用的sta044抗原能引发识别SEQ ID NO：80的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：80有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：80的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta044蛋白包括SEQ ID NO：80的变体。(b)的优选片段包含来自SEQ ID NO：80的表位。其它优选片段缺少SEQ ID NO：80的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：80的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：80的至少一个表位。SEQ ID NO：80的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta044 antigens are capable of eliciting antibodies that recognize SEQ ID NO:80 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:80 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:80, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta044 proteins include variants of SEQ ID NO:80. A preferred fragment of (b) comprises an epitope from SEQ ID NO:80. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 80 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 80, while retaining at least one epitope of SEQ ID NO:80. The first 17 N-terminal amino acids of SEQ ID NO:80 can be usefully omitted. Other fragments omit one or more protein domains.

sta045sta045

“sta045”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta045是SAOUHSC_01627，具有氨基酸序列SEQ ID NO：81(GI：88195337)。The "sta045" antigen is annotated as "lipoprotein". Among the NCTC 8325 strains, sta045 is SAOUHSC_01627, which has the amino acid sequence of SEQ ID NO: 81 (GI: 88195337).

有用的sta045抗原能引发识别SEQ ID NO：81的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：81有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：81的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta045蛋白包括SEQ ID NO：81的变体。(b)的优选片段包含来自SEQ ID NO：81的表位。其它优选片段缺少SEQ IDNO：81的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：81的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ IDNO：81的至少一个表位。SEQ ID NO：81的前16个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta045 antigens are capable of eliciting antibodies that recognize SEQ ID NO:81 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:81 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 81, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta045 proteins include variants of SEQ ID NO:81. A preferred fragment of (b) comprises an epitope from SEQ ID NO:81. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 81 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 81, and At least one epitope of SEQ ID NO:81 is retained. The first 16 N-terminal amino acids of SEQ ID NO: 81 can be usefully omitted. Other fragments omit one or more protein domains.

sta046sta046

“sta046”抗原注释为“Excalibur蛋白”。在NCTC 8325菌株中，sta046是SAOUHSC_01918，具有氨基酸序列SEQ ID NO：82(GI：88195613)。The "sta046" antigen is annotated as "Excalibur protein". In the NCTC 8325 strain, sta046 is SAOUHSC_01918, which has the amino acid sequence of SEQ ID NO: 82 (GI: 88195613).

有用的sta046抗原能引发识别SEQ ID NO：82的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：82有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：82的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta046蛋白包括SEQ ID NO：82的变体。(b)的优选片段包含来自SEQ ID NO：82的表位。其它优选片段缺少SEQ ID NO：82的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：82的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：82的至少一个表位。SEQ ID NO：82的前53个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta046 antigens are capable of eliciting antibodies that recognize SEQ ID NO:82 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:82 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:82, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta046 proteins include variants of SEQ ID NO:82. A preferred fragment of (b) comprises an epitope from SEQ ID NO:82. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 82 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 82, While retaining at least one epitope of SEQ ID NO:82. The first 53 N-terminal amino acids of SEQ ID NO: 82 can be usefully omitted. Other fragments omit one or more protein domains.

sta047sta047

“sta047”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta047是SAOUHSC_01920，具有氨基酸序列SEQ ID NO：83(GI：88195615)。The "sta047" antigen is annotated as "lipoprotein". In the NCTC 8325 strain, sta047 is SAOUHSC_01920, which has the amino acid sequence of SEQ ID NO: 83 (GI: 88195615).

有用的sta047抗原能引发识别SEQ ID NO：83的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：83有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：83的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta047蛋白包括SEQ ID NO：83的变体。(b)的优选片段包含来自SEQ ID NO：83的表位。其它优选片段缺少SEQ ID NO：83的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：83的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：83的至少一个表位。SEQ ID NO：83的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta047 antigens are capable of eliciting antibodies that recognize SEQ ID NO:83 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:83 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 83, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta047 proteins include variants of SEQ ID NO:83. A preferred fragment of (b) comprises an epitope from SEQ ID NO:83. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 83 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 83, While retaining at least one epitope of SEQ ID NO:83. The first 18 N-terminal amino acids of SEQ ID NO: 83 can be usefully omitted. Other fragments omit one or more protein domains.

sta048sta048

“sta048”抗原注释为“胞内丝氨酸蛋白酶”。在NCTC 8325菌株中，sta048是SAOUHSC_01949，具有氨基酸序列SEQ ID NO：84(GI：88195642)。The "sta048" antigen is annotated as "intracellular serine protease". In the NCTC 8325 strain, sta048 is SAOUHSC_01949, which has the amino acid sequence of SEQ ID NO: 84 (GI: 88195642).

有用的sta048抗原能引发识别SEQ ID NO：84的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：84有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：84的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta048蛋白包括SEQ ID NO：84的变体。(b)的优选片段包含来自SEQ ID NO：84的表位。其它优选片段缺少SEQ ID NO：84的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：84的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：84的至少一个表位。SEQ ID NO：84的前27个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta048 antigens are capable of eliciting antibodies that recognize SEQ ID NO:84 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:84 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 84, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta048 proteins include variants of SEQ ID NO:84. A preferred fragment of (b) comprises an epitope from SEQ ID NO:84. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 84 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 84, While retaining at least one epitope of SEQ ID NO:84. The first 27 N-terminal amino acids of SEQ ID NO: 84 can be usefully omitted. Other fragments omit one or more protein domains.

sta049sta049

“sta049”抗原注释为“蛋白质输出蛋白PrsA”。在NCTC 8325菌株中，sta049是SAOUHSC_01972，具有氨基酸序列SEQ ID NO：85(GI：88195663)。在Newman菌株中，其是nwmn_1733(GI：151221945)。The "sta049" antigen is annotated as "protein exporter PrsA". In the NCTC 8325 strain, sta049 is SAOUHSC_01972, which has the amino acid sequence of SEQ ID NO: 85 (GI: 88195663). In the Newman strain it is nwmn_1733 (GI: 151221945).

有用的sta049抗原能引发识别SEQ ID NO：85的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：85有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：85的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta049蛋白包括SEQ ID NO：85的变体。(b)的优选片段包含来自SEQ ID NO：85的表位。其它优选片段缺少SEQ ID NO：85的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：85的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：85的至少一个表位。SEQ ID NO：85的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta049 antigens are capable of eliciting antibodies that recognize SEQ ID NO:85 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:85 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 85, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta049 proteins include variants of SEQ ID NO:85. A preferred fragment of (b) comprises an epitope from SEQ ID NO:85. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 85 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 85, while retaining at least one epitope of SEQ ID NO:85. The first 25 N-terminal amino acids of SEQ ID NO: 85 can be usefully omitted. Other fragments omit one or more protein domains.

sta050sta050

“sta050”抗原注释为“司他弗平(staphopain)硫醇蛋白酶”。在NCTC8325菌株中，sta050是SAOUHSC_02127，具有氨基酸序列SEQ ID NO：86(GI：88195808)。The "sta050" antigen is annotated as "staphopain thiol protease". In the NCTC8325 strain, sta050 is SAOUHSC_02127, which has the amino acid sequence of SEQ ID NO: 86 (GI: 88195808).

有用的sta050抗原能引发识别SEQ ID NO：86的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：86有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：86的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta050蛋白包括SEQ ID NO：86的变体。(b)的优选片段包含来自SEQ ID NO：86的表位。其它优选片段缺少SEQ ID NO：86的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：86的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：86的至少一个表位。SEQ ID NO：86的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta050 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 86 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 86 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 86, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta050 proteins include variants of SEQ ID NO:86. A preferred fragment of (b) comprises an epitope from SEQ ID NO:86. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 86 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 86, While retaining at least one epitope of SEQ ID NO:86. The first 25 N-terminal amino acids of SEQ ID NO: 86 can be usefully omitted. Other fragments omit one or more protein domains.

sta051sta051

“sta051”抗原注释为“含前导序列的蛋白”。在NCTC 8325菌株中，sta051是SAOUHSC_02147，具有氨基酸序列SEQ ID NO：87(GI：88195827)。The "sta051" antigen is annotated as "leader-containing protein". Among the NCTC 8325 strains, sta051 is SAOUHSC_02147, which has the amino acid sequence of SEQ ID NO: 87 (GI: 88195827).

有用的sta051抗原能引发识别SEQ ID NO：87的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：87有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：87的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta051蛋白包括SEQ ID NO：87的变体。(b)的优选片段包含来自SEQ ID NO：87的表位。其它优选片段缺少SEQ ID NO：87的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：87的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：87的至少一个表位。SEQ ID NO：87的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta051 antigens are capable of eliciting antibodies that recognize SEQ ID NO:87 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:87 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 87, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta051 proteins include variants of SEQ ID NO:87. A preferred fragment of (b) comprises an epitope from SEQ ID NO:87. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 87 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 87, While retaining at least one epitope of SEQ ID NO:87. The first 24 N-terminal amino acids of SEQ ID NO: 87 can be usefully omitted. Other fragments omit one or more protein domains.

sta052sta052

“sta052”抗原注释为“氧肟酸铁受体1”。在NCTC 8325菌株中，sta052是SAOUHSC_02246，具有氨基酸序列SEQ ID NO：88(GI：88195918)。The "sta052" antigen is annotated as "iron hydroxamate receptor 1". In NCTC 8325 strain, sta052 is SAOUHSC_02246 with amino acid sequence SEQ ID NO: 88 (GI: 88195918).

有用的sta052抗原能引发识别SEQ ID NO：88的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：88有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：88的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta052蛋白包括SEQ ID NO：88的变体。(b)的优选片段包含来自SEQ ID NO：88的表位。其它优选片段缺少SEQ ID NO：88的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：88的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：88的至少一个表位。SEQ ID NO：88的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta052 antigens are capable of eliciting antibodies that recognize SEQ ID NO:88 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:88 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 88, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta052 proteins include variants of SEQ ID NO:88. A preferred fragment of (b) comprises an epitope from SEQ ID NO:88. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 88 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 88, While retaining at least one epitope of SEQ ID NO:88. The first 17 N-terminal amino acids of SEQ ID NO: 88 can be usefully omitted. Other fragments omit one or more protein domains.

sta053sta053

“sta053”抗原注释为“srdH家族蛋白”。在NCTC 8325菌株中，sta053是SAOUHSC_02257，具有氨基酸序列SEQ ID NO：89(GI：88195928)。The "sta053" antigen is annotated as "srdH family protein". In NCTC 8325 strain, sta053 is SAOUHSC_02257 with amino acid sequence SEQ ID NO: 89 (GI: 88195928).

有用的sta053抗原能引发识别SEQ ID NO：89的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：89有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：89的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta053蛋白包括SEQ ID NO：89的变体。(b)的优选片段包含来自SEQ ID NO：89的表位。其它优选片段缺少SEQ ID NO：89的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：89的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：89的至少一个表位。SEQ ID NO：89的前26个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta053 antigens are capable of eliciting antibodies that recognize SEQ ID NO:89 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:89 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 89, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta053 proteins include variants of SEQ ID NO:89. A preferred fragment of (b) comprises an epitope from SEQ ID NO:89. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 89 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 89, While retaining at least one epitope of SEQ ID NO:89. The first 26 N-terminal amino acids of SEQ ID NO: 89 can be usefully omitted. Other fragments omit one or more protein domains.

sta054sta054

“sta054”抗原注释为“可能的糖基转移酶isaA前体”。在NCTC 8325菌株中，sta054是SAOUHSC_02333，具有氨基酸序列SEQ ID NO：90(GI：88195999)。The "sta054" antigen is annotated as "probable precursor of the glycosyltransferase isaA". In NCTC 8325 strain, sta054 is SAOUHSC_02333 with amino acid sequence SEQ ID NO: 90 (GI: 88195999).

有用的sta054抗原能引发识别SEQ ID NO：90的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：90有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：90的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta054蛋白包括SEQ ID NO：90的变体。(b)的优选片段包含来自SEQ ID NO：90的表位。其它优选片段缺少SEQ ID NO：90的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：90的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：90的至少一个表位。SEQ ID NO：90的前27个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta054 antigens are capable of eliciting antibodies that recognize SEQ ID NO:90 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:90 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:90, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta054 proteins include variants of SEQ ID NO:90. A preferred fragment of (b) comprises an epitope from SEQ ID NO:90. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 90 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 90, While retaining at least one epitope of SEQ ID NO:90. The first 27 N-terminal amino acids of SEQ ID NO:90 can be usefully omitted. Other fragments omit one or more protein domains.

sta055sta055

“sta055”抗原注释为“表面水解酶”。在NCTC 8325菌株中，sta055是SAOUHSC_02448，具有氨基酸序列SEQ ID NO：91(GI：88196100)。The "sta055" antigen is annotated as "surface hydrolase". In the NCTC 8325 strain, sta055 is SAOUHSC_02448, which has the amino acid sequence of SEQ ID NO: 91 (GI: 88196100).

有用的sta055抗原能引发识别SEQ ID NO：91的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：91有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：91的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta055蛋白包括SEQ ID NO：91的变体。(b)的优选片段包含来自SEQ ID NO：91的表位。其它优选片段缺少SEQ ID NO：91的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：91的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：91的至少一个表位。SEQ ID NO：91的前31个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta055 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 91 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 91 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:91, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta055 proteins include variants of SEQ ID NO:91. A preferred fragment of (b) comprises an epitope from SEQ ID NO:91. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 91 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 91, While retaining at least one epitope of SEQ ID NO:91. The first 31 N-terminal amino acids of SEQ ID NO: 91 can be usefully omitted. Other fragments omit one or more protein domains.

sta056sta056

“sta056”抗原注释为“透明质酸裂合酶”。在NCTC 8325菌株中，sta056是SAOUHSC_02463，具有氨基酸序列SEQ ID NO：92(GI：88196115)。The "sta056" antigen is annotated as "hyaluronan lyase". In NCTC 8325 strain, sta056 is SAOUHSC_02463 with amino acid sequence SEQ ID NO: 92 (GI: 88196115).

有用的sta056抗原能引发识别SEQ ID NO：92的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：92有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：92的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta056蛋白包括SEQ ID NO：92的变体。(b)的优选片段包含来自SEQ ID NO：92的表位。其它优选片段缺少SEQ ID NO：92的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：92的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：92的至少一个表位。SEQ ID NO：92的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta056 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 92 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 92 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:92, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta056 proteins include variants of SEQ ID NO:92. A preferred fragment of (b) comprises an epitope from SEQ ID NO:92. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 92 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 92, While retaining at least one epitope of SEQ ID NO:92. The first 24 N-terminal amino acids of SEQ ID NO:92 can be usefully omitted. Other fragments omit one or more protein domains.

sta057sta057

“sta057”抗原注释为“分泌型抗原前体SsaA”。在NCTC 8325菌株中，sta057是SAOUHSC_02576，具有氨基酸序列SEQ ID NO：93(GI：88196220)。在Newman菌株中，其是nwmn_2203(GI：151222415)。The "sta057" antigen is annotated as "secreted precursor antigen SsaA". In NCTC 8325 strain, sta057 is SAOUHSC_02576 with amino acid sequence SEQ ID NO: 93 (GI: 88196220). In the Newman strain it is nwmn_2203 (GI: 151222415).

有用的sta057抗原能引发识别SEQ ID NO：93的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：93有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：93的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta057蛋白包括SEQ ID NO：93的变体。(b)的优选片段包含来自SEQ ID NO：93的表位。其它优选片段缺少SEQ IDNO：93的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：93的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ IDNO：93的至少一个表位。SEQ ID NO：93的前27个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta057 antigens are capable of eliciting antibodies that recognize SEQ ID NO:93 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:93 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:93, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta057 proteins include variants of SEQ ID NO:93. A preferred fragment of (b) comprises an epitope from SEQ ID NO:93. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 93 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 93, and At least one epitope of SEQ ID NO:93 is retained. The first 27 N-terminal amino acids of SEQ ID NO:93 can be usefully omitted. Other fragments omit one or more protein domains.

sta058sta058

“sta058”抗原注释为“Zn-结合脂蛋白adcA-样”。在NCTC 8325菌株中，sta058是SAOUHSC_02690，具有氨基酸序列SEQ ID NO：94(GI：88196330)。The "sta058" antigen was annotated as "Zn-binding lipoprotein adcA-like". In NCTC 8325 strain, sta058 is SAOUHSC_02690 with amino acid sequence SEQ ID NO: 94 (GI: 88196330).

有用的sta058抗原能引发识别SEQ ID NO：94的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：94有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：94的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta058蛋白包括SEQ ID NO：94的变体。(b)的优选片段包含来自SEQ ID NO：94的表位。其它优选片段缺少SEQ ID NO：94的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：94的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：94的至少一个表位。SEQ ID NO：94的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta058 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 94 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 94 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:94, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta058 proteins include variants of SEQ ID NO:94. A preferred fragment of (b) comprises an epitope from SEQ ID NO:94. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 94 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 94, While retaining at least one epitope of SEQ ID NO:94. The first 20 N-terminal amino acids of SEQ ID NO:94 can be usefully omitted. Other fragments omit one or more protein domains.

sta059sta059

“sta059”抗原注释为“γ-溶血素h-γ-ii亚单位”。在NCTC 8325菌株中，sta059是SAOUHSC_02708，具有氨基酸序列SEQ ID NO：95(GI：88196348)。The "sta059" antigen is annotated as "γ-hemolysin H-γ-II subunit". In the NCTC 8325 strain, sta059 is SAOUHSC_02708, which has the amino acid sequence of SEQ ID NO: 95 (GI: 88196348).

有用的sta059抗原能引发识别SEQ ID NO：95的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：95有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：95的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta059蛋白包括SEQ ID NO：95的变体。(b)的优选片段包含来自SEQ ID NO：95的表位。其它优选片段缺少SEQ ID NO：95的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：95的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：95的至少一个表位。SEQ ID NO：95的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta059 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 95 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 95 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:95, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta059 proteins include variants of SEQ ID NO:95. A preferred fragment of (b) comprises an epitope from SEQ ID NO:95. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 95 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 95, while retaining at least one epitope of SEQ ID NO:95. The first 20 N-terminal amino acids of SEQ ID NO:95 can be usefully omitted. Other fragments omit one or more protein domains.

sta060sta060

“sta060”抗原注释为“肽ABC转运蛋白；肽-结合蛋白”。在NCTC8325菌株中，sta060是SAOUHSC_02767，具有氨基酸序列SEQ ID NO：96(GI：88196403)。The "sta060" antigen is annotated as "peptide ABC transporter; peptide-binding protein". In the NCTC8325 strain, sta060 is SAOUHSC_02767, which has the amino acid sequence of SEQ ID NO: 96 (GI: 88196403).

有用的sta060抗原能引发识别SEQ ID NO：96的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：96有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：96的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta060蛋白包括SEQ ID NO：96的变体。(b)的优选片段包含来自SEQ ID NO：96的表位。其它优选片段缺少SEQ ID NO：96的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：96的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：96的至少一个表位。SEQ ID NO：96的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta060 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 96 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 96 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:96, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta060 proteins include variants of SEQ ID NO:96. A preferred fragment of (b) comprises an epitope from SEQ ID NO:96. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 96 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 96, While retaining at least one epitope of SEQ ID NO:96. The first 20 N-terminal amino acids of SEQ ID NO:96 can be usefully omitted. Other fragments omit one or more protein domains.

sta061sta061

“sta061”抗原注释为“含前导序列的蛋白”。在NCTC 8325菌株中，sta061是SAOUHSC_02783，具有氨基酸序列SEQ ID NO：97(GI：88196419)。The "sta061" antigen is annotated as "leader-containing protein". In the NCTC 8325 strain, sta061 is SAOUHSC_02783, which has the amino acid sequence of SEQ ID NO: 97 (GI: 88196419).

有用的sta061抗原能引发识别SEQ ID NO：97的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：97有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：97的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta061蛋白包括SEQ ID NO：97的变体。(b)的优选片段包含来自SEQ ID NO：97的表位。其它优选片段缺少SEQ ID NO：97的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：97的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：97的至少一个表位。SEQ ID NO：97的前21个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta061 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 97 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 97 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:97, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta061 proteins include variants of SEQ ID NO:97. A preferred fragment of (b) comprises an epitope from SEQ ID NO:97. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 97 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 97, while retaining at least one epitope of SEQ ID NO:97. The first 21 N-terminal amino acids of SEQ ID NO:97 can be usefully omitted. Other fragments omit one or more protein domains.

sta062sta062

“sta062”抗原注释为“含前导序列的蛋白”。在NCTC 8325菌株中，sta062是SAOUHSC_02788，具有氨基酸序列SEQ ID NO：98(GI：88196424)。The "sta062" antigen is annotated as "leader-containing protein". In the NCTC 8325 strain, sta062 is SAOUHSC_02788, which has the amino acid sequence of SEQ ID NO: 98 (GI: 88196424).

有用的sta062抗原能引发识别SEQ ID NO：98的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：98有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：98的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta062蛋白包括SEQ ID NO：98的变体。(b)的优选片段包含来自SEQ ID NO：98的表位。其它优选片段缺少SEQ ID NO：98的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：98的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：98的至少一个表位。SEQ ID NO：98的前22个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta062 antigens are capable of eliciting antibodies that recognize SEQ ID NO:98 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:98 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:98, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta062 proteins include variants of SEQ ID NO:98. A preferred fragment of (b) comprises an epitope from SEQ ID NO:98. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 98 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 98, While retaining at least one epitope of SEQ ID NO:98. The first 22 N-terminal amino acids of SEQ ID NO:98 can be usefully omitted. Other fragments omit one or more protein domains.

sta063sta063

“sta063”抗原注释为“金溶素(aureolysin)”。在NCTC 8325菌株中，sta063是SAOUHSC_02971，具有氨基酸序列SEQ ID NO：99(GI：88196592)。The "sta063" antigen is annotated as "aureolysin". In NCTC 8325 strain, sta063 is SAOUHSC_02971 with amino acid sequence SEQ ID NO: 99 (GI: 88196592).

有用的sta063抗原能引发识别SEQ ID NO：99的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：99有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：99的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta063蛋白包括SEQ ID NO：99的变体。(b)的优选片段包含来自SEQ ID NO：99的表位。其它优选片段缺少SEQ ID NO：99的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：99的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：99的至少一个表位。SEQ ID NO：99的前16个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta063 antigens are capable of eliciting antibodies that recognize SEQ ID NO:99 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO:99 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO:99, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta063 proteins include variants of SEQ ID NO:99. A preferred fragment of (b) comprises an epitope from SEQ ID NO:99. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 99 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 99, While retaining at least one epitope of SEQ ID NO:99. The first 16 N-terminal amino acids of SEQ ID NO:99 can be usefully omitted. Other fragments omit one or more protein domains.

sta064sta064

“sta064”抗原注释为“脂肪酶”。在NCTC 8325菌株中，sta064是SAOUHSC_03006，具有氨基酸序列SEQ ID NO：100(GI：88196625)。在Newman菌株中，其是nwmn_2569(GI：151222781)。The "sta064" antigen is annotated as "lipase". In the NCTC 8325 strain, sta064 is SAOUHSC_03006, which has the amino acid sequence of SEQ ID NO: 100 (GI: 88196625). In the Newman strain it is nwmn_2569 (GI: 151222781 ).

有用的sta064抗原能引发识别SEQ ID NO：100的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：100有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：100的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta064蛋白包括SEQ ID NO：100的变体。(b)的优选片段包含来自SEQ ID NO：100的表位。其它优选片段缺少SEQ ID NO：100的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：100的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：100的至少一个表位。SEQ ID NO：100的前34个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta064 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 100 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 100 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 100, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta064 proteins include variants of SEQ ID NO:100. A preferred fragment of (b) comprises an epitope from SEQ ID NO:100. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 100 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 100, While retaining at least one epitope of SEQ ID NO: 100. The first 34 N-terminal amino acids of SEQ ID NO: 100 can be usefully omitted. Other fragments omit one or more protein domains.

sta065sta065

“sta065”抗原注释为“1-磷脂酰肌醇磷酸二酯酶前体”。在NCTC 8325菌株中，sta065是SAOUHSC_00051，具有氨基酸序列SEQ ID NO：101(GI：88193871)。The "sta065" antigen is annotated as "1-phosphatidylinositol phosphodiesterase precursor". In the NCTC 8325 strain, sta065 is SAOUHSC_00051, which has the amino acid sequence of SEQ ID NO: 101 (GI: 88193871).

有用的sta065抗原能引发识别SEQ ID NO：101的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：101有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：101的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta065蛋白包括SEQ ID NO：101的变体。(b)的优选片段包含来自SEQ ID NO：101的表位。其它优选片段缺少SEQ ID NO：101的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：101的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：101的至少一个表位。SEQ ID NO：101的前26个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta065 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 101 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 101 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 101, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta065 proteins include variants of SEQ ID NO:101. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 101. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 101 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 101, While retaining at least one epitope of SEQ ID NO: 101. The first 26 N-terminal amino acids of SEQ ID NO: 101 can be usefully omitted. Other fragments omit one or more protein domains.

sta066sta066

“sta066”抗原注释为“蛋白质”。在NCTC 8325菌株中，sta066是SAOUHSC_00172，具有氨基酸序列SEQ ID NO：102(GI：88193982)。The "sta066" antigen is annotated as "protein". In NCTC 8325 strain, sta066 is SAOUHSC_00172 with amino acid sequence SEQ ID NO: 102 (GI: 88193982).

有用的sta066抗原能引发识别SEQ ID NO：102的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：102有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：102的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta066蛋白包括SEQ ID NO：102的变体。(b)的优选片段包含来自SEQ ID NO：102的表位。其它优选片段缺少SEQ ID NO：102的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：102的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：102的至少一个表位。SEQ ID NO：102的前21个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta066 antigens can elicit antibodies that recognize SEQ ID NO: 102 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 102 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 102, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta066 proteins include variants of SEQ ID NO:102. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 102. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 102 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 102, While retaining at least one epitope of SEQ ID NO: 102. The first 21 N-terminal amino acids of SEQ ID NO: 102 can be usefully omitted. Other fragments omit one or more protein domains.

sta067sta067

“sta067”抗原注释为“细菌胞外溶质-结合蛋白质”。在NCTC 8325菌株中，sta067是SAOUHSC_00176，具有氨基酸序列SEQ ID NO：103(GI：88193986)。The "sta067" antigen is annotated as "bacterial extracellular solute-binding protein". In the NCTC 8325 strain, sta067 is SAOUHSC_00176, which has the amino acid sequence of SEQ ID NO: 103 (GI: 88193986).

有用的sta067抗原能引发识别SEQ ID NO：103的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：103有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：103的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta067蛋白包括SEQ ID NO：103的变体。(b)的优选片段包含来自SEQ ID NO：103的表位。其它优选片段缺少SEQ ID NO：103的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：103的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：103的至少一个表位。SEQ ID NO：103的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta067 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 103 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 103 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 103, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta067 proteins include variants of SEQ ID NO:103. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 103. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 103 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 103, While retaining at least one epitope of SEQ ID NO: 103. The first 20 N-terminal amino acids of SEQ ID NO: 103 can be usefully omitted. Other fragments omit one or more protein domains.

sta068sta068

“sta068”抗原注释为“铁通透酶FTR1”。在NCTC 8325菌株中，sta068是SAOUHSC_00327，具有氨基酸序列SEQ ID NO：104(GI：88194127)。The "sta068" antigen is annotated as "iron permease FTR1". In NCTC 8325 strain, sta068 is SAOUHSC_00327 with amino acid sequence SEQ ID NO: 104 (GI: 88194127).

有用的sta068抗原能引发识别SEQ ID NO：104的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：104有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：104的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta068蛋白包括SEQ ID NO：104的变体。(b)的优选片段包含来自SEQ ID NO：104的表位。其它优选片段缺少SEQ ID NO：104的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：104的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：104的至少一个表位。SEQ ID NO：104的最后20个C-末端氨基酸可有用地省去。SEQ ID NO：104的前14个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta068 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 104 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 104 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 104, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta068 proteins include variants of SEQ ID NO:104. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 104. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 104 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 104, While retaining at least one epitope of SEQ ID NO: 104. The last 20 C-terminal amino acids of SEQ ID NO: 104 can be usefully omitted. The first 14 N-terminal amino acids of SEQ ID NO: 104 can be usefully omitted. Other fragments omit one or more protein domains.

sta069sta069

“sta069”抗原注释为“自溶素前体”。在NCTC 8325菌株中，sta069是SAOUHSC_00427，具有氨基酸序列SEQ ID NO：105(GI：88194219)。The "sta069" antigen is annotated as "autolysin precursor". In the NCTC 8325 strain, sta069 is SAOUHSC_00427, which has the amino acid sequence of SEQ ID NO: 105 (GI: 88194219).

有用的sta069抗原能引发识别SEQ ID NO：105的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：105有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：105的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta069蛋白包括SEQ ID NO：105的变体。(b)的优选片段包含来自SEQ ID NO：105的表位。其它优选片段缺少SEQ ID NO：105的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：105的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：105的至少一个表位。SEQ ID NO：105的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta069 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 105 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 105 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 105, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta069 proteins include variants of SEQ ID NO:105. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 105. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 105 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 105, While retaining at least one epitope of SEQ ID NO: 105. The first 25 N-terminal amino acids of SEQ ID NO: 105 can be usefully omitted. Other fragments omit one or more protein domains.

sta070sta070

“sta070”抗原注释为“免疫原性分泌型前体样蛋白(截短的)”。在NCTC 8325菌株中，sta070是SAOUHSC_00773，具有氨基酸序列SEQ IDNO：106(GI：88194535)。The "sta070" antigen is annotated as "Immunogenic secreted precursor-like protein (truncated)". In NCTC 8325 strain, sta070 is SAOUHSC_00773 with amino acid sequence SEQ ID NO: 106 (GI: 88194535).

有用的sta070抗原能引发识别SEQ ID NO：106的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：106有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：106的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta070蛋白包括SEQ ID NO：106的变体。(b)的优选片段包含来自SEQ ID NO：106的表位。其它优选片段缺少SEQ ID NO：106的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：106的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：106的至少一个表位。SEQ ID NO：106的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta070 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 106 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 106 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 106, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta070 proteins include variants of SEQ ID NO:106. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 106. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 106 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 106, While retaining at least one epitope of SEQ ID NO: 106. The first 24 N-terminal amino acids of SEQ ID NO: 106 can be usefully omitted. Other fragments omit one or more protein domains.

sta071sta071

“sta071”抗原注释为“溶血素”。在NCTC 8325菌株中，sta071是SAOUHSC_00854，具有氨基酸序列SEQ ID NO：107(GI：88194612)。The "sta071" antigen is annotated as "hemolysin". In the NCTC 8325 strain, sta071 is SAOUHSC_00854, which has the amino acid sequence of SEQ ID NO: 107 (GI: 88194612).

有用的sta071抗原能引发识别SEQ ID NO：107的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：107有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：107的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta071蛋白包括SEQ ID NO：107的变体。(b)的优选片段包含来自SEQ ID NO：107的表位。其它优选片段缺少SEQ ID NO：107的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：107的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：107的至少一个表位。SEQ ID NO：107的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta071 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 107 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 107 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 107, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta071 proteins include variants of SEQ ID NO:107. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 107. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 107 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 107, While retaining at least one epitope of SEQ ID NO: 107. The first 24 N-terminal amino acids of SEQ ID NO: 107 can be usefully omitted. Other fragments omit one or more protein domains.

sta072sta072

“sta072”抗原注释为“膜外蛋白”。在NCTC 8325菌株中，sta072是SAOUHSC_00872，具有氨基酸序列SEQ ID NO：108(GI：88194629)。The "sta072" antigen is annotated as "outer membrane protein". In NCTC 8325 strain, sta072 is SAOUHSC_00872 with amino acid sequence SEQ ID NO: 108 (GI: 88194629).

有用的sta072抗原能引发识别SEQ ID NO：108的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：108有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：108的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta072蛋白包括SEQ ID NO：108的变体。(b)的优选片段包含来自SEQ ID NO：108的表位。其它优选片段缺少SEQ ID NO：108的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：108的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：108的至少一个表位。SEQ ID NO：108的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta072 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 108 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 108 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 108, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta072 proteins include variants of SEQ ID NO:108. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 108. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 108 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 108, While retaining at least one epitope of SEQ ID NO: 108. The first 24 N-terminal amino acids of SEQ ID NO: 108 can be usefully omitted. Other fragments omit one or more protein domains.

sta073sta073

“sta073”抗原注释为“双功能自溶素前体”。在NCTC 8325菌株中，sta073是SAOUHSC_00994，具有氨基酸序列SEQ ID NO：109(GI：88194750)。在Newman菌株中，其是nwmn_0922(GI：151221134)。蛋白质组分析揭示该蛋白是分泌或表面暴露的蛋白。The "sta073" antigen is annotated as "bifunctional autolysin precursor". In NCTC 8325 strain, sta073 is SAOUHSC_00994 with amino acid sequence SEQ ID NO: 109 (GI: 88194750). In the Newman strain it is nwmn_0922 (GI: 151221134). Proteome analysis revealed that the protein was secreted or surface exposed.

有用的sta073抗原能引发识别SEQ ID NO：109的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：109有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：109的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta073蛋白包括SEQ ID NO：109的变体。(b)的优选片段包含来自SEQ ID NO：109的表位。其它优选片段缺少SEQ ID NO：109的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：109的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：109的至少一个表位。SEQ ID NO：109的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta073 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 109 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 109 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 109, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta073 proteins include variants of SEQ ID NO:109. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 109. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 109 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 109, While retaining at least one epitope of SEQ ID NO: 109. The first 24 N-terminal amino acids of SEQ ID NO: 109 can be usefully omitted. Other fragments omit one or more protein domains.

Sta073抗原可有用地与Sta112组合包含在组合物中[74]。The Sta073 antigen may usefully be included in compositions in combination with Sta112 [74].

Sta073不能良好吸附于氢氧化铝佐剂，因此组合物中存在的Sta073可以是不吸附的或可吸附于其它佐剂，例如吸附于磷酸铝。Sta073 does not adsorb well to aluminum hydroxide adjuvants, therefore Sta073 present in the composition may be unadsorbed or adsorbable to other adjuvants, for example to aluminum phosphate.

sta074sta074

“sta074”抗原注释为“甲氧西林耐药至关重要的因子”。在NCTC 8325菌株中，sta074是SAOUHSC_01220，具有氨基酸序列SEQ ID NO：110(GI：88194956)。The "sta074" antigen is annotated as "a critical factor for methicillin resistance". In the NCTC 8325 strain, sta074 is SAOUHSC_01220, which has the amino acid sequence of SEQ ID NO: 110 (GI: 88194956).

有用的sta074抗原能引发识别SEQ ID NO：110的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：110有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：110的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta074蛋白包括SEQ ID NO：110的变体。(b)的优选片段包含来自SEQ ID NO：110的表位。其它优选片段缺少SEQ ID NO：110的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：110的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：110的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta074 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 110 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 110 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 110, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta074 proteins include variants of SEQ ID NO:110. A preferred fragment of (b) comprises an epitope from SEQ ID NO:110. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 110 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 110, While retaining at least one epitope of SEQ ID NO: 110. Other fragments omit one or more protein domains.

sta075sta075

“sta075”抗原注释为“胰岛素酶(insulysin)；肽酶家族M16”。在NCTC8325菌株中，sta075是SAOUHSC_01256，具有氨基酸序列SEQ ID NO：111(GI：88194989)。The "sta075" antigen is annotated as "insulysin; peptidase family M16". In the NCTC8325 strain, sta075 is SAOUHSC_01256, which has the amino acid sequence of SEQ ID NO: 111 (GI: 88194989).

有用的sta075抗原能引发识别SEQ ID NO：111的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：111有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：111的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta075蛋白包括SEQ ID NO：111的变体。(b)的优选片段包含来自SEQ ID NO：111的表位。其它优选片段缺少SEQ ID NO：111的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：111的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：111的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta075 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 111 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 111 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 111, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta075 proteins include variants of SEQ ID NO:111. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 111. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 111 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 111, While retaining at least one epitope of SEQ ID NO: 111. Other fragments omit one or more protein domains.

sta076sta076

“sta076”抗原注释为“水解酶”。在NCTC 8325菌株中，sta076是SAOUHSC_01263，具有氨基酸序列SEQ ID NO：112(GI：88194996)。The "sta076" antigen is annotated as "hydrolase". In the NCTC 8325 strain, sta076 is SAOUHSC_01263, which has the amino acid sequence of SEQ ID NO: 112 (GI: 88194996).

有用的sta076抗原能引发识别SEQ ID NO：112的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：112有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：112的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta076蛋白包括SEQ ID NO：112的变体。(b)的优选片段包含来自SEQ ID NO：112的表位。其它优选片段缺少SEQ ID NO：112的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：112的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：112的至少一个表位。SEQ ID NO：112的前24个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta076 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 112 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 112 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 112, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta076 proteins include variants of SEQ ID NO:112. A preferred fragment of (b) comprises an epitope from SEQ ID NO:112. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 112 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 112, While retaining at least one epitope of SEQ ID NO: 112. The first 24 N-terminal amino acids of SEQ ID NO: 112 can be usefully omitted. Other fragments omit one or more protein domains.

sta077sta077

“sta077”抗原注释为“蛋白质”。在NCTC 8325菌株中，sta077是SAOUHSC_01317，具有氨基酸序列SEQ ID NO：113(GI：88195047)。蛋白质组分析揭示该蛋白是分泌或表面暴露的。The "sta077" antigen is annotated as "protein". In the NCTC 8325 strain, sta077 is SAOUHSC_01317, which has the amino acid sequence of SEQ ID NO: 113 (GI: 88195047). Proteome analysis revealed that the protein was either secreted or surface exposed.

有用的sta077抗原能引发识别SEQ ID NO：113的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：113有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：113的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta077蛋白包括SEQ ID NO：113的变体。(b)的优选片段包含来自SEQ ID NO：113的表位。其它优选片段缺少SEQ ID NO：113的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：113的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：113的至少一个表位。SEQ ID NO：113的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta077 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 113 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 113 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 113, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta077 proteins include variants of SEQ ID NO:113. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 113. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 113 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 113, While retaining at least one epitope of SEQ ID NO: 113. The first 20 N-terminal amino acids of SEQ ID NO: 113 can be usefully omitted. Other fragments omit one or more protein domains.

sta078sta078

“sta078”抗原注释为“FtsK/SpoIIIE家族蛋白”。在NCTC 8325菌株中，sta078是SAOUHSC_01857，具有氨基酸序列SEQ ID NO：114(GI：88195555)。The "sta078" antigen is annotated as "FtsK/SpoIIIE family protein". In the NCTC 8325 strain, sta078 is SAOUHSC_01857, which has the amino acid sequence of SEQ ID NO: 114 (GI: 88195555).

有用的sta078抗原能引发识别SEQ ID NO：114的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：114有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：114的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta078蛋白包括SEQ ID NO：114的变体。(b)的优选片段包含来自SEQ ID NO：114的表位。其它优选片段缺少SEQ ID NO：114的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：114的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：114的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta078 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 114 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 114 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 114, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta078 proteins include variants of SEQ ID NO:114. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 114. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 114 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 114, While retaining at least one epitope of SEQ ID NO: 114. Other fragments omit one or more protein domains.

sta079sta079

“sta079”抗原注释为“丝氨酸蛋白酶SplF”。在NCTC 8325菌株中，sta079是SAOUHSC_01935，具有氨基酸序列SEQ ID NO：115(GI：88195630)。The "sta079" antigen is annotated as "serine protease SplF". Among the NCTC 8325 strains, sta079 is SAOUHSC_01935, which has the amino acid sequence of SEQ ID NO: 115 (GI: 88195630).

有用的sta079抗原能引发识别SEQ ID NO：115的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：115有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：115的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta079蛋白包括SEQ ID NO：115的变体。(b)的优选片段包含来自SEQ ID NO：115的表位。其它优选片段缺少SEQ ID NO：115的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：115的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：115的至少一个表位。SEQ ID NO：115的前36个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta079 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 115 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 115 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 115, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta079 proteins include variants of SEQ ID NO:115. A preferred fragment of (b) comprises an epitope from SEQ ID NO:115. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 115 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 115, while retaining at least one epitope of SEQ ID NO: 115. The first 36 N-terminal amino acids of SEQ ID NO: 115 can be usefully omitted. Other fragments omit one or more protein domains.

sta080sta080

“sta080”抗原注释为“丝氨酸蛋白酶SplE”。在NCTC 8325菌株中，sta080是SAOUHSC_01936，具有氨基酸序列SEQ ID NO：116(GI：88195631)。The "sta080" antigen is annotated as "serine protease SplE". In the NCTC 8325 strain, sta080 is SAOUHSC_01936, which has the amino acid sequence of SEQ ID NO: 116 (GI: 88195631).

有用的sta080抗原能引发识别SEQ ID NO：116的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：116有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：116的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta080蛋白包括SEQ ID NO：116的变体。(b)的优选片段包含来自SEQ ID NO：116的表位。其它优选片段缺少SEQ ID NO：116的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：116的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：116的至少一个表位。SEQ ID NO：116的前36个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta080 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 116 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 116 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 116, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta080 proteins include variants of SEQ ID NO:116. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 116. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 116 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 116, While retaining at least one epitope of SEQ ID NO: 116. The first 36 N-terminal amino acids of SEQ ID NO: 116 can be usefully omitted. Other fragments omit one or more protein domains.

sta081sta081

“sta081”抗原注释为“丝氨酸蛋白酶SplD(EC：3.4.21.19)”。在NCTC8325菌株中，sta081是SAOUHSC_01938，具有氨基酸序列SEQ ID NO：170(GI：88195633)。The "sta081" antigen is annotated as "serine protease SpID (EC: 3.4.21.19)". In the NCTC8325 strain, sta081 is SAOUHSC_01938, which has the amino acid sequence of SEQ ID NO: 170 (GI: 88195633).

有用的sta081抗原能引发识别SEQ ID NO：170的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：170有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：170的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta081蛋白包括SEQ ID NO：170的变体。(b)的优选片段包含来自SEQ ID NO：170的表位。其它优选片段缺少SEQ ID NO：170的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：170的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：170的至少一个表位。SEQ ID NO：170的前36个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta081 antigens can elicit antibodies that recognize SEQ ID NO: 170 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 170 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 170, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta081 proteins include variants of SEQ ID NO:170. A preferred fragment of (b) comprises an epitope from SEQ ID NO:170. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 170 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 170, While retaining at least one epitope of SEQ ID NO: 170. The first 36 N-terminal amino acids of SEQ ID NO: 170 can be usefully omitted. Other fragments omit one or more protein domains.

sta082sta082

“sta082”抗原注释为“丝氨酸蛋白酶SplC”。在NCTC 8325菌株中，sta082是SAOUHSC_01939，具有氨基酸序列SEQ ID NO：117(GI：88195634)。The "sta082" antigen is annotated as "serine protease SplC". In the NCTC 8325 strain, sta082 is SAOUHSC_01939, which has the amino acid sequence of SEQ ID NO: 117 (GI: 88195634).

有用的sta082抗原能引发识别SEQ ID NO：117的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：117有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：117的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta082蛋白包括SEQ ID NO：117的变体。(b)的优选片段包含来自SEQ ID NO：117的表位。其它优选片段缺少SEQ ID NO：117的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：117的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：117的至少一个表位。SEQ ID NO：117的前36个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta082 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 117 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 117 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 117, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta082 proteins include variants of SEQ ID NO:117. A preferred fragment of (b) comprises an epitope from SEQ ID NO:117. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 117 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 117, while retaining at least one epitope of SEQ ID NO: 117. The first 36 N-terminal amino acids of SEQ ID NO: 117 can be usefully omitted. Other fragments omit one or more protein domains.

sta083sta083

“sta083”抗原注释为“丝氨酸蛋白酶SplB”。在NCTC 8325菌株中，sta083是SAOUHSC_01941，具有氨基酸序列SEQ ID NO：118(GI：88195635)。The "sta083" antigen is annotated as "serine protease SplB". In the NCTC 8325 strain, sta083 is SAOUHSC_01941, which has the amino acid sequence of SEQ ID NO: 118 (GI: 88195635).

有用的sta083抗原能引发识别SEQ ID NO：118的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：118有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：118的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta083蛋白包括SEQ ID NO：118的变体。(b)的优选片段包含来自SEQ ID NO：118的表位。其它优选片段缺少SEQ ID NO：118的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：118的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：118的至少一个表位。SEQ ID NO：118的前36个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta083 antigens can elicit antibodies that recognize SEQ ID NO: 118 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 118 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 118, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta083 proteins include variants of SEQ ID NO:118. A preferred fragment of (b) comprises an epitope from SEQ ID NO:118. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 118 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 118, While retaining at least one epitope of SEQ ID NO: 118. The first 36 N-terminal amino acids of SEQ ID NO: 118 can be usefully omitted. Other fragments omit one or more protein domains.

sta084sta084

“sta084”抗原注释为“丝氨酸蛋白酶SplA”。在NCTC 8325菌株中，sta084是SAOUHSC_01942，具有氨基酸序列SEQ ID NO：119(GI：88195636)。The "sta084" antigen is annotated as "serine protease SplA". In the NCTC 8325 strain, sta084 is SAOUHSC_01942, which has the amino acid sequence of SEQ ID NO: 119 (GI: 88195636).

有用的sta084抗原能引发识别SEQ ID NO：119的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：119有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：119的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta084蛋白包括SEQ ID NO：119的变体。(b)的优选片段包含来自SEQ ID NO：119的表位。其它优选片段缺少SEQ ID NO：119的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：119的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：119的至少一个表位。SEQ ID NO：119的前35个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta084 antigens can elicit antibodies that recognize SEQ ID NO: 119 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 119 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 119, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta084 proteins include variants of SEQ ID NO:119. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 119. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 119 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 119, While retaining at least one epitope of SEQ ID NO: 119. The first 35 N-terminal amino acids of SEQ ID NO: 119 can be usefully omitted. Other fragments omit one or more protein domains.

sta085sta085

“sta085”抗原注释为“葡萄球菌激酶前体”。在NCTC 8325菌株中，sta085是SAOUHSC_02171，具有氨基酸序列SEQ ID NO：120(GI：88195848)。The "sta085" antigen is annotated as "staphylokinase precursor". Among the NCTC 8325 strains, sta085 is SAOUHSC_02171 with the amino acid sequence of SEQ ID NO: 120 (GI: 88195848).

有用的sta085抗原能引发识别SEQ ID NO：120的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：120有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：120的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta085蛋白包括SEQ ID NO：120的变体。(b)的优选片段包含来自SEQ ID NO：120的表位。其它优选片段缺少SEQ ID NO：120的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：120的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：120的至少一个表位。SEQ ID NO：120的前27个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta085 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 120 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 120 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 120, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta085 proteins include variants of SEQ ID NO:120. A preferred fragment of (b) comprises an epitope from SEQ ID NO:120. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 120 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 120, While retaining at least one epitope of SEQ ID NO:120. The first 27 N-terminal amino acids of SEQ ID NO: 120 can be usefully omitted. Other fragments omit one or more protein domains.

sta086sta086

“sta086”抗原注释为“OxaA-样蛋白”。在NCTC 8325菌株中，sta086是SAOUHSC_02327，具有氨基酸序列SEQ ID NO：121(GI：88195993)。The "sta086" antigen is annotated as "OxaA-like protein". In the NCTC 8325 strain, sta086 is SAOUHSC_02327, which has the amino acid sequence of SEQ ID NO: 121 (GI: 88195993).

有用的sta086抗原能引发识别SEQ ID NO：121的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：121有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：121的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta086蛋白包括SEQ ID NO：121的变体。(b)的优选片段包含来自SEQ ID NO：121的表位。其它优选片段缺少SEQ ID NO：121的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：121的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：121的至少一个表位。SEQ ID NO：121的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta086 antigens can elicit antibodies that recognize SEQ ID NO: 121 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 121 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 121, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta086 proteins include variants of SEQ ID NO:121. A preferred fragment of (b) comprises an epitope from SEQ ID NO:121. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 121 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 121, While retaining at least one epitope of SEQ ID NO: 121. The first 19 N-terminal amino acids of SEQ ID NO: 121 can be usefully omitted. Other fragments omit one or more protein domains.

sta087sta087

“sta087”抗原注释为“替考拉宁耐受蛋白TcaA”。在NCTC 8325菌株中，sta087是SAOUHSC_02635，具有氨基酸序列SEQ ID NO：122(GI：88196276)。The "sta087" antigen is annotated as "teicoplanin resistance protein TcaA". Among the NCTC 8325 strains, sta087 is SAOUHSC_02635, which has the amino acid sequence of SEQ ID NO: 122 (GI: 88196276).

有用的sta087抗原能引发识别SEQ ID NO：122的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：122有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：122的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta087蛋白包括SEQ ID NO：122的变体。(b)的优选片段包含来自SEQ ID NO：122的表位。其它优选片段缺少SEQ ID NO：122的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：122的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：122的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta087 antigens can elicit antibodies that recognize SEQ ID NO: 122 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 122 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 122, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta087 proteins include variants of SEQ ID NO:122. A preferred fragment of (b) comprises an epitope from SEQ ID NO:122. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 122 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 122, While retaining at least one epitope of SEQ ID NO: 122. Other fragments omit one or more protein domains.

sta088sta088

“sta088”抗原注释为“酯酶”。在NCTC 8325菌株中，sta088是SAOUHSC_02844，具有氨基酸序列SEQ ID NO：123(GI：88196477)。The "sta088" antigen is annotated as "esterase". In the NCTC 8325 strain, sta088 is SAOUHSC_02844, which has the amino acid sequence of SEQ ID NO: 123 (GI: 88196477).

有用的sta088抗原能引发识别SEQ ID NO：123的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：123有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：123的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta088蛋白包括SEQ ID NO：123的变体。(b)的优选片段包含来自SEQ ID NO：123的表位。其它优选片段缺少SEQ ID NO：123的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：123的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：123的至少一个表位。SEQ ID NO：123的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta088 antigens can elicit antibodies that recognize SEQ ID NO: 123 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 123 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 123, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta088 proteins include variants of SEQ ID NO:123. A preferred fragment of (b) comprises an epitope from SEQ ID NO:123. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 123 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 123, While retaining at least one epitope of SEQ ID NO: 123. The first 18 N-terminal amino acids of SEQ ID NO: 123 can be usefully omitted. Other fragments omit one or more protein domains.

sta089sta089

“sta089”抗原注释为“LysM结构域蛋白”。在NCTC 8325菌株中，sta089是SAOUHSC_02855，具有氨基酸序列SEQ ID NO：124(GI：88196486)。The "sta089" antigen is annotated as "LysM domain protein". In the NCTC 8325 strain, sta089 is SAOUHSC_02855, which has the amino acid sequence of SEQ ID NO: 124 (GI: 88196486).

有用的sta089抗原能引发识别SEQ ID NO：124的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：124有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：124的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta089蛋白包括SEQ ID NO：124的变体。(b)的优选片段包含来自SEQ ID NO：124的表位。其它优选片段缺少SEQ IDNO：124的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：124的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：124的至少一个表位。SEQ ID NO：124的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta089 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 124 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 124 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 124, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta089 proteins include variants of SEQ ID NO:124. A preferred fragment of (b) comprises an epitope from SEQ ID NO:124. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 124 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 124, and At least one epitope of SEQ ID NO: 124 is retained. The first 20 N-terminal amino acids of SEQ ID NO: 124 can be usefully omitted. Other fragments omit one or more protein domains.

sta090sta090

“sta090”抗原注释为“LysM结构域蛋白”。在NCTC 8325菌株中，sta090是SAOUHSC_02883，具有氨基酸序列SEQ ID NO：125(GI：88196512)。The "sta090" antigen is annotated as "LysM domain protein". In NCTC 8325 strain, sta090 is SAOUHSC_02883 with amino acid sequence SEQ ID NO: 125 (GI: 88196512).

有用的sta090抗原能引发识别SEQ ID NO：125的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：125有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：125的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta090蛋白包括SEQ ID NO：125的变体。(b)的优选片段包含来自SEQ ID NO：125的表位。其它优选片段缺少SEQ ID NO：125的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：125的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：125的至少一个表位。SEQ ID NO：125的前26个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta090 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 125 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 125 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 125, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta090 proteins include variants of SEQ ID NO:125. A preferred fragment of (b) comprises an epitope from SEQ ID NO:125. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 125 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 125, While retaining at least one epitope of SEQ ID NO: 125. The first 26 N-terminal amino acids of SEQ ID NO: 125 can be usefully omitted. Other fragments omit one or more protein domains.

sta091sta091

“sta091”抗原注释为“脂蛋白”。在NCTC 8325菌株中，sta091是SAOUHSC_00685，具有氨基酸序列SEQ ID NO：126(GI：88194450)。The "sta091" antigen is annotated as "lipoprotein". Among the NCTC 8325 strains, sta091 is SAOUHSC_00685, which has the amino acid sequence of SEQ ID NO: 126 (GI: 88194450).

有用的sta091抗原能引发识别SEQ ID NO：126的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：126有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：126的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta091蛋白包括SEQ ID NO：126的变体。(b)的优选片段包含来自SEQ ID NO：126的表位。其它优选片段缺少SEQ IDNO：126的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：126的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：126的至少一个表位。SEQ ID NO：126的前15个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta091 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 126 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 126 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 126, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta091 proteins include variants of SEQ ID NO:126. A preferred fragment of (b) comprises an epitope from SEQ ID NO:126. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 126 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 126, and At least one epitope of SEQ ID NO: 126 is retained. The first 15 N-terminal amino acids of SEQ ID NO: 126 can be usefully omitted. Other fragments omit one or more protein domains.

sta092sta092

“sta092”抗原注释为“M23/M37肽酶结构域蛋白”。在NCTC 8325菌株中，sta092是SAOUHSC_00174，具有氨基酸序列SEQ ID NO：127(GI：88193984)。The "sta092" antigen is annotated as "M23/M37 peptidase domain protein". In the NCTC 8325 strain, sta092 is SAOUHSC_00174, which has the amino acid sequence of SEQ ID NO: 127 (GI: 88193984).

有用的sta092抗原能引发识别SEQ ID NO：127的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：127有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：127的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta092蛋白包括SEQ ID NO：127的变体。(b)的优选片段包含来自SEQ ID NO：127的表位。其它优选片段缺少SEQ ID NO：127的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：127的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：127的至少一个表位。SEQ ID NO：127的前25个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta092 antigens can elicit antibodies that recognize SEQ ID NO: 127 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 127 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 127, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta092 proteins include variants of SEQ ID NO:127. A preferred fragment of (b) comprises an epitope from SEQ ID NO:127. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 127 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 127, while retaining at least one epitope of SEQ ID NO: 127. The first 25 N-terminal amino acids of SEQ ID NO: 127 can be usefully omitted. Other fragments omit one or more protein domains.

sta093sta093

“sta093”抗原注释为“蛋白质”。在NCTC 8325菌株中，sta093是SAOUHSC_01854，具有氨基酸序列SEQ ID NO：128(GI：88195552)。The "sta093" antigen is annotated as "protein". In the NCTC 8325 strain, sta093 is SAOUHSC_01854, which has the amino acid sequence of SEQ ID NO: 128 (GI: 88195552).

有用的sta093抗原能引发识别SEQ ID NO：128的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：128有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：128的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta093蛋白包括SEQ ID NO：128的变体。(b)的优选片段包含来自SEQ ID NO：128的表位。其它优选片段缺少SEQ ID NO：128的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：128的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：128的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta093 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 128 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 128 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 128, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta093 proteins include variants of SEQ ID NO:128. A preferred fragment of (b) comprises an epitope from SEQ ID NO:128. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 128 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 128, While retaining at least one epitope of SEQ ID NO: 128. Other fragments omit one or more protein domains.

sta094sta094

“sta094”抗原注释为“蛋白质”。在NCTC 8325菌株中，sta094是SAOUHSC_01512，具有氨基酸序列SEQ ID NO：129(GI：88195226)。The "sta094" antigen is annotated as "protein". In the NCTC 8325 strain, sta094 is SAOUHSC_01512, which has the amino acid sequence of SEQ ID NO: 129 (GI: 88195226).

有用的sta094抗原能引发识别SEQ ID NO：129的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：129有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：129的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta094蛋白包括SEQ ID NO：129的变体。(b)的优选片段包含来自SEQ ID NO：129的表位。其它优选片段缺少SEQ ID NO：129的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：129的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：129的至少一个表位。SEQ ID NO：129的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta094 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 129 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 129 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 129, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta094 proteins include variants of SEQ ID NO:129. A preferred fragment of (b) comprises an epitope from SEQ ID NO:129. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 129 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 129, While retaining at least one epitope of SEQ ID NO: 129. The first 17 N-terminal amino acids of SEQ ID NO: 129 can be usefully omitted. Other fragments omit one or more protein domains.

sta095sta095

“sta095”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta095是SAOUHSC_00383，具有氨基酸序列SEQ ID NO：130(GI：88194180)。在Newman菌株中，其是nwmn_0388(GI：151220600)。The "sta095" antigen is annotated as a "superantigen-like protein". Among the NCTC 8325 strains, sta095 is SAOUHSC_00383, which has the amino acid sequence of SEQ ID NO: 130 (GI: 88194180). In the Newman strain it is nwmn_0388 (GI: 151220600).

有用的sta095抗原能引发识别SEQ ID NO：130的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：130有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：130的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta095蛋白包括SEQ ID NO：130的变体。(b)的优选片段包含来自SEQ ID NO：130的表位。其它优选片段缺少SEQ ID NO：130的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：130的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：130的至少一个表位。SEQ ID NO：130的前32个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta095 antigens can elicit antibodies that recognize SEQ ID NO: 130 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 130 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 130, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta095 proteins include variants of SEQ ID NO:130. A preferred fragment of (b) comprises an epitope from SEQ ID NO:130. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 130 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 130, While retaining at least one epitope of SEQ ID NO: 130. The first 32 N-terminal amino acids of SEQ ID NO: 130 can be usefully omitted. Other fragments omit one or more protein domains.

sta096sta096

“sta096”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta096是SAOUHSC_00384，具有氨基酸序列SEQ ID NO：131(GI：88194181)。The "sta096" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta096 is SAOUHSC_00384, which has the amino acid sequence of SEQ ID NO: 131 (GI: 88194181).

有用的sta096抗原能引发识别SEQ ID NO：131的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：131有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：131的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta096蛋白包括SEQ ID NO：131的变体。(b)的优选片段包含来自SEQ ID NO：131的表位。其它优选片段缺少SEQ ID NO：131的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：131的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：131的至少一个表位。SEQ ID NO：131的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。A useful sta096 antigen is capable of eliciting antibodies recognizing SEQ ID NO: 131 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 131 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 131, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta096 proteins include variants of SEQ ID NO:131. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 131. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 131 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 131, While retaining at least one epitope of SEQ ID NO: 131. The first 30 N-terminal amino acids of SEQ ID NO: 131 can be usefully omitted. Other fragments omit one or more protein domains.

sta097sta097

“sta097”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta097是SAOUHSC_00386，具有氨基酸序列SEQ ID NO：132(GI：88194182)。The "sta097" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta097 is SAOUHSC_00386, which has the amino acid sequence of SEQ ID NO: 132 (GI: 88194182).

有用的sta097抗原能引发识别SEQ ID NO：132的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：132有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：132的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta097蛋白包括SEQ ID NO：132的变体。(b)的优选片段包含来自SEQ ID NO：132的表位。其它优选片段缺少SEQ ID NO：132的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：132的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：132的至少一个表位。SEQ ID NO：132的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta097 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 132 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 132 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 132, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta097 proteins include variants of SEQ ID NO:132. A preferred fragment of (b) comprises an epitope from SEQ ID NO:132. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 132 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 132, While retaining at least one epitope of SEQ ID NO: 132. The first 30 N-terminal amino acids of SEQ ID NO: 132 can be usefully omitted. Other fragments omit one or more protein domains.

sta098sta098

“sta098”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta098是SAOUHSC_00389，具有氨基酸序列SEQ ID NO：133(GI：88194184)。在Newman菌株中，其是nwmn_0391(GI：151220603)。The "sta098" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta098 is SAOUHSC_00389, which has the amino acid sequence of SEQ ID NO: 133 (GI: 88194184). In the Newman strain it is nwmn_0391 (GI: 151220603).

有用的sta098抗原能引发识别SEQ ID NO：133的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：133有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：133的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta098蛋白包括SEQ ID NO：133的变体。(b)的优选片段包含来自SEQ ID NO：133的表位。其它优选片段缺少SEQ ID NO：133的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：133的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：133的至少一个表位。SEQ ID NO：133的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta098 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 133 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 133 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 133, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta098 proteins include variants of SEQ ID NO:133. A preferred fragment of (b) comprises an epitope from SEQ ID NO:133. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 133 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 133, While retaining at least one epitope of SEQ ID NO: 133. The first 30 N-terminal amino acids of SEQ ID NO: 133 can be usefully omitted. Other fragments omit one or more protein domains.

sta099sta099

“sta099”抗原注释为“超抗原-样蛋白5”。在NCTC 8325菌株中，sta099是SAOUHSC_00390，具有氨基酸序列SEQ ID NO：134(GI：88194185)。The "sta099" antigen is annotated as "superantigen-like protein 5". In NCTC 8325 strain, sta099 is SAOUHSC_00390 with amino acid sequence SEQ ID NO: 134 (GI: 88194185).

有用的sta099抗原能引发识别SEQ ID NO：134的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：134有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：134的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta099蛋白包括SEQ ID NO：134的变体。(b)的优选片段包含来自SEQ ID NO：134的表位。其它优选片段缺少SEQ ID NO：134的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：134的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：134的至少一个表位。SEQ ID NO：134的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta099 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 134 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 134 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 134, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta099 proteins include variants of SEQ ID NO:134. A preferred fragment of (b) comprises an epitope from SEQ ID NO:134. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 134 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 134, While retaining at least one epitope of SEQ ID NO: 134. The first 30 N-terminal amino acids of SEQ ID NO: 134 can be usefully omitted. Other fragments omit one or more protein domains.

Sta100Sta100

“sta100”抗原注释为“超抗原-样蛋白5”。在NCTC 8325菌株中，sta100是SAOUHSC_00391，具有氨基酸序列SEQ ID NO：135(GI：88194186)。The "sta100" antigen is annotated as "superantigen-like protein 5". In the NCTC 8325 strain, sta100 is SAOUHSC_00391, which has the amino acid sequence of SEQ ID NO: 135 (GI: 88194186).

有用的sta100抗原能引发识别SEQ ID NO：135的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：135有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：135的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta100蛋白包括SEQ ID NO：135的变体。(b)的优选片段包含来自SEQ ID NO：135的表位。其它优选片段缺少SEQ ID NO：135的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：135的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：135的至少一个表位。SEQ ID NO：135的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta100 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 135 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 135 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 135, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta100 proteins include variants of SEQ ID NO:135. A preferred fragment of (b) comprises an epitope from SEQ ID NO:135. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 135 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 135, While retaining at least one epitope of SEQ ID NO: 135. The first 30 N-terminal amino acids of SEQ ID NO: 135 can be usefully omitted. Other fragments omit one or more protein domains.

Sta101Sta101

“sta101”抗原注释为“超抗原-样蛋白7”。在NCTC 8325菌株中，sta101是SAOUHSC_00392，具有氨基酸序列SEQ ID NO：136(GI：88194187)。在Newman菌株中，其是nwmn_0394(GI：151220606)。The "sta101" antigen is annotated as "superantigen-like protein 7". In the NCTC 8325 strain, sta101 is SAOUHSC_00392, which has the amino acid sequence of SEQ ID NO: 136 (GI: 88194187). In the Newman strain it is nwmn_0394 (GI: 151220606).

有用的sta101抗原能引发识别SEQ ID NO：136的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：136有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：136的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta101蛋白包括SEQ ID NO：136的变体。(b)的优选片段包含来自SEQ ID NO：136的表位。其它优选片段缺少SEQ ID NO：136的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：136的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：136的至少一个表位。SEQ ID NO：136的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta101 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 136 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 136 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 136, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta101 proteins include variants of SEQ ID NO:136. A preferred fragment of (b) comprises an epitope from SEQ ID NO:136. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 136 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 136, While retaining at least one epitope of SEQ ID NO: 136. The first 30 N-terminal amino acids of SEQ ID NO: 136 can be usefully omitted. Other fragments omit one or more protein domains.

Sta102Sta102

“sta102”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta102是SAOUHSC_00393，具有氨基酸序列SEQ ID NO：137(GI：88194188)。The "sta102" antigen is annotated as a "superantigen-like protein". In NCTC 8325 strain, sta102 is SAOUHSC_00393 with amino acid sequence SEQ ID NO: 137 (GI: 88194188).

有用的sta102抗原能引发识别SEQ ID NO：137的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：137有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：137的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta102蛋白包括SEQ ID NO：137的变体。(b)的优选片段包含来自SEQ ID NO：137的表位。其它优选片段缺少SEQ ID NO：137的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：137的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：137的至少一个表位。SEQ ID NO：137的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta102 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 137 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 137 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 137, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta102 proteins include variants of SEQ ID NO:137. A preferred fragment of (b) comprises an epitope from SEQ ID NO:137. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 137 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 137, While retaining at least one epitope of SEQ ID NO: 137. The first 17 N-terminal amino acids of SEQ ID NO: 137 can be usefully omitted. Other fragments omit one or more protein domains.

Sta103Sta103

“sta103”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta103是SAOUHSC_00394，具有氨基酸序列SEQ ID NO：138(GI：88194189)。The "sta103" antigen is annotated as a "superantigen-like protein". In NCTC 8325 strain, sta103 is SAOUHSC_00394, which has the amino acid sequence of SEQ ID NO: 138 (GI: 88194189).

有用的sta103抗原能引发识别SEQ ID NO：138的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：138有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：138的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta103蛋白包括SEQ ID NO：138的变体。(b)的优选片段包含来自SEQ ID NO：138的表位。其它优选片段缺少SEQ ID NO：138的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：138的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：138的至少一个表位。SEQ ID NO：138的前23个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta103 antigens elicit antibodies that recognize SEQ ID NO: 138 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 138 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 138, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta103 proteins include variants of SEQ ID NO:138. A preferred fragment of (b) comprises an epitope from SEQ ID NO:138. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 138 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 138, While retaining at least one epitope of SEQ ID NO: 138. The first 23 N-terminal amino acids of SEQ ID NO: 138 can be usefully omitted. Other fragments omit one or more protein domains.

Sta104Sta104

“sta104”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta104是SAOUHSC_00395，具有氨基酸序列SEQ ID NO：139(GI：88194190)。The "sta104" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta104 is SAOUHSC_00395, which has the amino acid sequence of SEQ ID NO: 139 (GI: 88194190).

有用的sta104抗原能引发识别SEQ ID NO：139的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：139有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：139的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta104蛋白包括SEQ ID NO：139的变体。(b)的优选片段包含来自SEQ ID NO：139的表位。其它优选片段缺少SEQ ID NO：139的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：139的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：139的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta104 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 139 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 139 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 139, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta104 proteins include variants of SEQ ID NO:139. A preferred fragment of (b) comprises an epitope from SEQ ID NO:139. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 139 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 139, While retaining at least one epitope of SEQ ID NO: 139. Other fragments omit one or more protein domains.

Sta105Sta105

“sta105”抗原注释为“超抗原-样蛋白”。在NCTC 8325菌株中，sta105是SAOUHSC_00399，具有氨基酸序列SEQ ID NO：140(GI：88194194)。在Newman菌株中，其是nwmn_0400(GI：151220612)。The "sta105" antigen is annotated as a "superantigen-like protein". In the NCTC 8325 strain, sta105 is SAOUHSC_00399, which has the amino acid sequence of SEQ ID NO: 140 (GI: 88194194). In the Newman strain it is nwmn_0400 (GI: 151220612).

有用的sta105抗原能引发识别SEQ ID NO：140的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：140有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：140的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta105蛋白包括SEQ ID NO：140的变体。(b)的优选片段包含来自SEQ ID NO：140的表位。其它优选片段缺少SEQ ID NO：140的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：140的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：140的至少一个表位。SEQ ID NO：140的前30个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta105 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 140 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 140 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 140, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta105 proteins include variants of SEQ ID NO:140. A preferred fragment of (b) comprises an epitope from SEQ ID NO:140. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 140 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 140, while retaining at least one epitope of SEQ ID NO:140. The first 30 N-terminal amino acids of SEQ ID NO: 140 can be usefully omitted. Other fragments omit one or more protein domains.

Sta106Sta106

“sta106”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta106是SAOUHSC_01115，具有氨基酸序列SEQ ID NO：141(GI：88194861)。The "sta106" antigen is annotated as a "putative protein". In the NCTC 8325 strain, sta106 is SAOUHSC_01115, which has the amino acid sequence of SEQ ID NO: 141 (GI: 88194861).

有用的sta106抗原能引发识别SEQ ID NO：141的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：141有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：141的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta106蛋白包括SEQ ID NO：141的变体。(b)的优选片段包含来自SEQ ID NO：141的表位。其它优选片段缺少SEQ IDNO：141的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：141的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：141的至少一个表位。SEQ ID NO：141的前16个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta106 antigens elicit antibodies that recognize SEQ ID NO: 141 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 141 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 141, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta106 proteins include variants of SEQ ID NO:141. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 141. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 141 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 141, and At least one epitope of SEQ ID NO: 141 is retained. The first 16 N-terminal amino acids of SEQ ID NO: 141 can be usefully omitted. Other fragments omit one or more protein domains.

Sta107Sta107

“sta107”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta107是SAOUHSC_00354，具有氨基酸序列SEQ ID NO：177(GI：88194153)。The "sta107" antigen is annotated as a "putative protein". In NCTC 8325 strain, sta107 is SAOUHSC_00354, which has the amino acid sequence of SEQ ID NO: 177 (GI: 88194153).

有用的sta107抗原能引发识别SEQ ID NO：177的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：177有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：177的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta107蛋白包括SEQ ID NO：177的变体。(b)的优选片段包含来自SEQ ID NO：177的表位。其它优选片段缺少SEQ ID NO：177的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：177的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：177的至少一个表位。SEQ ID NO：177的前35个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta107 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 177 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 177 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 177, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta107 proteins include variants of SEQ ID NO:177. A preferred fragment of (b) comprises an epitope from SEQ ID NO:177. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 177 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 177, While retaining at least one epitope of SEQ ID NO: 177. The first 35 N-terminal amino acids of SEQ ID NO: 177 can be usefully omitted. Other fragments omit one or more protein domains.

Sta108Sta108

“sta108”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta108是SAOUHSC_00717，具有氨基酸序列SEQ ID NO：178(GI：88194482)。The "sta108" antigen is annotated as a "putative protein". In the NCTC 8325 strain, sta108 is SAOUHSC_00717, which has the amino acid sequence of SEQ ID NO: 178 (GI: 88194482).

有用的sta108抗原能引发识别SEQ ID NO：178的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：178有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：178的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta108蛋白包括SEQ ID NO：178的变体。(b)的优选片段包含来自SEQ ID NO：178的表位。其它优选片段缺少SEQ IDNO：178的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：178的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：178的至少一个表位。SEQ ID NO：178的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta108 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 178 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 178 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 178, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta108 proteins include variants of SEQ ID NO:178. A preferred fragment of (b) comprises an epitope from SEQ ID NO:178. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 178 and /or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 178, and At least one epitope of SEQ ID NO: 178 is retained. The first 20 N-terminal amino acids of SEQ ID NO: 178 can be usefully omitted. Other fragments omit one or more protein domains.

Sta109Sta109

“sta109”抗原注释为“N-乙酰基胞壁酰基-L-丙氨酸酰胺酶”。在NCTC8325菌株中，sta109是SAOUHSC_02979，具有氨基酸序列SEQ ID NO：179(GI：88196599)。The "sta109" antigen is annotated as "N-acetylmuramoyl-L-alanine amidase". In the NCTC8325 strain, sta109 is SAOUHSC_02979, which has the amino acid sequence of SEQ ID NO: 179 (GI: 88196599).

有用的sta109抗原能引发识别SEQ ID NO：179的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：179有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：179的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta109蛋白包括SEQ ID NO：179的变体。(b)的优选片段包含来自SEQ ID NO：179的表位。其它优选片段缺少SEQ ID NO：179的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：179的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：179的至少一个表位。SEQ ID NO：179的前27个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta109 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 179 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 179 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 179, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta109 proteins include variants of SEQ ID NO:179. A preferred fragment of (b) comprises an epitope from SEQ ID NO:179. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 179 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 179, While retaining at least one epitope of SEQ ID NO: 179. The first 27 N-terminal amino acids of SEQ ID NO: 179 can be usefully omitted. Other fragments omit one or more protein domains.

Sta110Sta110

“sta110”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta110是SAOUHSC_01039，具有氨基酸序列SEQ ID NO：180(GI：88194791)。The "sta110" antigen is annotated as a "putative protein". In the NCTC 8325 strain, sta110 is SAOUHSC_01039, which has the amino acid sequence of SEQ ID NO: 180 (GI: 88194791).

有用的sta110抗原能引发识别SEQ ID NO：180的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：180有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：180的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些sta110蛋白包括SEQ ID NO：180的变体。(b)的优选片段包含来自SEQ ID NO：180的表位。其它优选片段缺少SEQ ID NO：180的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：180的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：180的至少一个表位。SEQ ID NO：180的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta110 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 180 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 180 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 180, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These sta110 proteins include variants of SEQ ID NO:180. A preferred fragment of (b) comprises an epitope from SEQ ID NO:180. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 180 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 180, While retaining at least one epitope of SEQ ID NO: 180. The first 19 N-terminal amino acids of SEQ ID NO: 180 can be usefully omitted. Other fragments omit one or more protein domains.

Sta111Sta111

“sta111”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta111是SAOUHSC_01005，具有氨基酸序列SEQ ID NO：181(GI：88194760)。The "sta111" antigen is annotated as a "putative protein". Among the NCTC 8325 strains, sta111 is SAOUHSC_01005, which has the amino acid sequence of SEQ ID NO: 181 (GI: 88194760).

有用的sta111抗原能引发识别SEQ ID NO：181的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：181有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：181的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta111蛋白包括SEQ ID NO：181的变体。(b)的优选片段包含来自SEQ ID NO：181的表位。其它优选片段缺少SEQ IDNO：181的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：181的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：181的至少一个表位。SEQ ID NO：181的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta111 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 181 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 181 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 181, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta111 proteins include variants of SEQ ID NO:181. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 181. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 181 and /or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 181, and At least one epitope of SEQ ID NO: 181 is retained. The first 20 N-terminal amino acids of SEQ ID NO: 181 can be usefully omitted. Other fragments omit one or more protein domains.

Sta112Sta112

“sta112”抗原注释为推定的“ABC转运蛋白，底物结合蛋白”。在NCTC 8325菌株中，sta112是SAOUHSC_00634，具有氨基酸序列SEQ IDNO：182(GI：88194402)。The "sta112" antigen is annotated as a putative "ABC transporter, substrate binding protein". In NCTC 8325 strain, sta112 is SAOUHSC_00634, which has the amino acid sequence of SEQ ID NO: 182 (GI: 88194402).

有用的sta112抗原能引发识别SEQ ID NO：182的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：182有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：182的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta112蛋白包括SEQ ID NO：182的变体。(b)的优选片段包含来自SEQ ID NO：182的表位。其它优选片段缺少SEQ ID NO：182的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：182的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：182的至少一个表位。SEQ ID NO：182的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta112 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 182 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 182 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 182, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta112 proteins include variants of SEQ ID NO:182. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 182. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 182 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 182, While retaining at least one epitope of SEQ ID NO: 182. The first 17 N-terminal amino acids of SEQ ID NO: 182 can be usefully omitted. Other fragments omit one or more protein domains.

Sta112抗原可有用地与Sta073组合包含在组合物中[74]。The Sta112 antigen may usefully be included in compositions in combination with Sta073 [74].

Sta113Sta113

“sta113”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta113是SAOUHSC_00728，具有氨基酸序列SEQ ID NO：183(GI：88194493)。The "sta113" antigen is annotated as a "putative protein". In the NCTC 8325 strain, sta113 is SAOUHSC_00728, which has the amino acid sequence of SEQ ID NO: 183 (GI: 88194493).

有用的sta113抗原能引发识别SEQ ID NO：183的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：183有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：183的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta113蛋白包括SEQ ID NO：183的变体。(b)的优选片段包含来自SEQ ID NO：183的表位。其它优选片段缺少SEQ ID NO：183的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：183的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：183的至少一个表位。SEQ ID NO：183的前173个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta113 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 183 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 183 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 183, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta113 proteins include variants of SEQ ID NO:183. A preferred fragment of (b) comprises an epitope from SEQ ID NO:183. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 183 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 183, While retaining at least one epitope of SEQ ID NO: 183. The first 173 N-terminal amino acids of SEQ ID NO: 183 can be usefully omitted. Other fragments omit one or more protein domains.

Sta114Sta114

“sta114”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta114是SAOUHSC_00810，具有氨基酸序列SEQ ID NO：184(GI：88194570)。The "sta114" antigen is annotated as a "putative protein". In the NCTC 8325 strain, sta114 is SAOUHSC_00810, which has the amino acid sequence of SEQ ID NO: 184 (GI: 88194570).

有用的sta114抗原能引发识别SEQ ID NO：184的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：184有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：184的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta114蛋白包括SEQ ID NO：184的变体。(b)的优选片段包含来自SEQ ID NO：184的表位。其它优选片段缺少SEQ ID NO：184的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：184的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：184的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta114 antigens elicit antibodies that recognize SEQ ID NO: 184 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 184 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 184, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta114 proteins include variants of SEQ ID NO:184. A preferred fragment of (b) comprises an epitope from SEQ ID NO:184. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 184 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 184, While retaining at least one epitope of SEQ ID NO: 184. Other fragments omit one or more protein domains.

Sta115Sta115

“sta115”抗原注释为“假定的蛋白”。在NCTC 8325菌株中，sta115是SAOUHSC_00817，具有氨基酸序列SEQ ID NO：185(GI：88194576)。The "sta115" antigen is annotated as a "putative protein". In the NCTC 8325 strain, sta115 is SAOUHSC_00817, which has the amino acid sequence of SEQ ID NO: 185 (GI: 88194576).

有用的sta115抗原能引发识别SEQ ID NO：185的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：185有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：185的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta115蛋白包括SEQ ID NO：185的变体。(b)的优选片段包含来自SEQ ID NO：185的表位。其它优选片段缺少SEQ ID NO：185的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：185的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：185的至少一个表位。SEQ ID NO：185的前18个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta115 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 185 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 185 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 185, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta115 proteins include variants of SEQ ID NO:185. A preferred fragment of (b) comprises an epitope from SEQ ID NO:185. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 185 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 185, while retaining at least one epitope of SEQ ID NO: 185. The first 18 N-terminal amino acids of SEQ ID NO: 185 can be usefully omitted. Other fragments omit one or more protein domains.

Sta116Sta116

“sta116”抗原注释为“甲酰基肽受体-样1抑制蛋白”。在NCTC 8325菌株中，sta116是SAOUHSC_01112，具有氨基酸序列SEQ ID NO：186(GI：88194858)。The "sta116" antigen is annotated as "formyl peptide receptor-like 1 inhibitory protein". In the NCTC 8325 strain, sta116 is SAOUHSC_01112, which has the amino acid sequence of SEQ ID NO: 186 (GI: 88194858).

有用的sta116抗原能引发识别SEQ ID NO：186的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：186有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：186的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta116蛋白包括SEQ ID NO：186的变体。(b)的优选片段包含来自SEQ ID NO：186的表位。其它优选片段缺少SEQ IDNO：186的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：186的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：186的至少一个表位。SEQ ID NO：186的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful sta116 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 186 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 186 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 186, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta116 proteins include variants of SEQ ID NO:186. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 186. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 186 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 186, and At least one epitope of SEQ ID NO: 186 is retained. The first 20 N-terminal amino acids of SEQ ID NO: 186 can be usefully omitted. Other fragments omit one or more protein domains.

Sta117Sta117

“sta117”抗原注释为“截短的β-溶血素”。在NCTC 8325菌株中，sta117是SAOUHSC_02240，具有氨基酸序列SEQ ID NO：187(GI：88195913)。The "sta117" antigen is annotated as "truncated β-hemolysin". In the NCTC 8325 strain, sta117 is SAOUHSC_02240, which has the amino acid sequence of SEQ ID NO: 187 (GI: 88195913).

有用的sta117抗原能引发识别SEQ ID NO：187的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：187有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：187的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta117蛋白包括SEQ ID NO：187的变体。(b)的优选片段包含来自SEQ ID NO：187的表位。其它优选片段缺少SEQ ID NO：187的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：187的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：187的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta117 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 187 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 187 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 187, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta117 proteins include variants of SEQ ID NO:187. A preferred fragment of (b) comprises an epitope from SEQ ID NO:187. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 187 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 187, while retaining at least one epitope of SEQ ID NO: 187. Other fragments omit one or more protein domains.

Sta118Sta118

“sta118”抗原注释为“细胞分裂蛋白FtsZ”。在NCTC 8325菌株中，sta118是SAOUHSC_01150，具有氨基酸序列SEQ ID NO：188(GI：88194892)。The "sta118" antigen is annotated as "cell division protein FtsZ". In the NCTC 8325 strain, sta118 is SAOUHSC_01150, which has the amino acid sequence of SEQ ID NO: 188 (GI: 88194892).

有用的sta118抗原能引发识别SEQ ID NO：188的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：188有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：188的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些sta118蛋白包括SEQ ID NO：188的变体。(b)的优选片段包含来自SEQ ID NO：188的表位。其它优选片段缺少SEQ ID NO：188的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：188的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：188的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta118 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 188 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 188 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 188, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These sta118 proteins include variants of SEQ ID NO:188. A preferred fragment of (b) comprises an epitope from SEQ ID NO: 188. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 188 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 188, While retaining at least one epitope of SEQ ID NO: 188. Other fragments omit one or more protein domains.

Sta119Sta119

“sta119”抗原注释为“硫氧还蛋白”。在NCTC 8325菌株中，sta119是SAOUHSC_01100，具有氨基酸序列SEQ ID NO：200(GI：88194846)。The "sta119" antigen is annotated as "thioredoxin". In the NCTC 8325 strain, sta119 is SAOUHSC_01100, which has the amino acid sequence of SEQ ID NO: 200 (GI: 88194846).

有用的sta119抗原能引发识别SEQ ID NO：200的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：200有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：200的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些sta119蛋白包括SEQ ID NO：200的变体。(b)的优选片段包含来自SEQ ID NO：200的表位。其它优选片段缺少SEQ IDNO：200的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：200的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：200的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta119 antigens are capable of eliciting antibodies that recognize SEQ ID NO: 200 (e.g., when administered to a human) and/or may comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 200 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 200, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These sta119 proteins include variants of SEQ ID NO:200. A preferred fragment of (b) comprises an epitope from SEQ ID NO:200. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 200 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminus of SEQ ID NO: 200, and At least one epitope of SEQ ID NO: 200 is retained. Other fragments omit one or more protein domains.

Sta120Sta120

“sta120”抗原注释为“烷基过氧化氢还原酶亚单位C”。在NCTC 8325菌株中，sta120是SAOUHSC_00365，具有氨基酸序列SEQ ID NO：201(GI：88194163)。The "sta120" antigen is annotated as "Alkyl Hydrogen Peroxide Reductase Subunit C". In the NCTC 8325 strain, sta120 is SAOUHSC_00365, which has the amino acid sequence of SEQ ID NO: 201 (GI: 88194163).

有用的sta120抗原能引发识别SEQ ID NO：201的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：201有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：201的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些sta120蛋白包括SEQ ID NO：201的变体。(b)的优选片段包含来自SEQ ID NO：201的表位。其它优选片段缺少SEQ ID NO：201的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：201的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：201的至少一个表位。其它片段省去一个或多个蛋白质结构域。Useful sta120 antigens can elicit antibodies that recognize SEQ ID NO: 201 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 201 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 201, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These sta120 proteins include variants of SEQ ID NO:201. A preferred fragment of (b) comprises an epitope from SEQ ID NO:201. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 201 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 201, While retaining at least one epitope of SEQ ID NO: 201. Other fragments omit one or more protein domains.

NW_6NW_6

“NW_6”抗原注释为“分泌型von Willebrand因子-结合蛋白前体”。在Newman菌株中，NW_6是NWMN_0757，具有氨基酸序列SEQ ID NO：142(GI：151220969)。The "NW_6" antigen is annotated as "secreted von Willebrand factor-binding protein precursor". In the Newman strain, NW_6 is NWMN_0757, having the amino acid sequence of SEQ ID NO: 142 (GI: 151220969).

有用的NW_6抗原能引发识别SEQ ID NO：142的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：142有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：142的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些NW_6蛋白包括SEQ ID NO：142的变体。(b)的优选片段包含来自SEQ ID NO：142的表位。其它优选片段缺少SEQ ID NO：142的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：142的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：142的至少一个表位。SEQ ID NO：142的前13个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_6 antigens can elicit antibodies that recognize SEQ ID NO: 142 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 142 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 142, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These NW_6 proteins include variants of SEQ ID NO: 142. A preferred fragment of (b) comprises an epitope from SEQ ID NO:142. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 142 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 142, While retaining at least one epitope of SEQ ID NO: 142. The first 13 N-terminal amino acids of SEQ ID NO: 142 can be usefully omitted. Other fragments omit one or more protein domains.

NW_9NW_9

“NW_9”抗原注释为“脂蛋白”。在Newman菌株中，NW_9是NWMN_0958，具有氨基酸序列SEQ ID NO：143(GI：151221170)。The "NW_9" antigen is annotated as "lipoprotein". In the Newman strain, NW_9 is NWMN_0958, having the amino acid sequence of SEQ ID NO: 143 (GI: 151221170).

有用的NW_9抗原能引发识别SEQ ID NO：143的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：143有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：143的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200或更高)。这些NW_9蛋白包括SEQ ID NO：143的变体。(b)的优选片段包含来自SEQ ID NO：143的表位。其它优选片段缺少SEQ ID NO：143的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：143的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：143的至少一个表位。SEQ ID NO：143的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_9 antigens can elicit antibodies that recognize SEQ ID NO: 143 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 143 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 143, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or higher). These NW_9 proteins include variants of SEQ ID NO:143. A preferred fragment of (b) comprises an epitope from SEQ ID NO:143. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 143 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 143, While retaining at least one epitope of SEQ ID NO: 143. The first 19 N-terminal amino acids of SEQ ID NO: 143 can be usefully omitted. Other fragments omit one or more protein domains.

NW_10NW_10

“NW_10”抗原注释为“纤维蛋白原结合-相关蛋白”。在Newman菌株中，NW_10是NWMN_1066，具有氨基酸序列SEQ ID NO：144(GI：151221278)。The "NW_10" antigen is annotated as "Fibrinogen Binding-Associated Protein". In the Newman strain, NW_10 is NWMN_1066, having the amino acid sequence of SEQ ID NO: 144 (GI: 151221278).

有用的NW_10抗原能引发识别SEQ ID NO：144的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：144有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：144的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些NW_10蛋白包括SEQ ID NO：144的变体。(b)的优选片段包含来自SEQ ID NO：144的表位。其它优选片段缺少SEQ IDNO：144的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：144的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：144的至少一个表位。SEQ ID NO：144的前20个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_10 antigens can elicit antibodies that recognize SEQ ID NO: 144 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 144 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 144, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These NW_10 proteins include variants of SEQ ID NO:144. A preferred fragment of (b) comprises an epitope from SEQ ID NO:144. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 144 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 144, and At least one epitope of SEQ ID NO: 144 is retained. The first 20 N-terminal amino acids of SEQ ID NO: 144 can be usefully omitted. Other fragments omit one or more protein domains.

NW_7NW_7

“NW_7”抗原注释为“葡萄球菌补体抑制剂SCIN”。在Newman菌株中，NW_7是NWMN_1876，具有氨基酸序列SEQ ID NO：145(GI：151222088)。The "NW_7" antigen is annotated as "Staphylococcal complement inhibitor SCIN". In the Newman strain, NW_7 is NWMN_1876, having the amino acid sequence of SEQ ID NO: 145 (GI: 151222088).

有用的NW_7抗原能引发识别SEQ ID NO：145的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：145有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：145的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些NW_7蛋白包括SEQ ID NO：145的变体。(b)的优选片段包含来自SEQ ID NO：145的表位。其它优选片段缺少SEQ IDNO：145的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：145的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：145的至少一个表位。SEQ ID NO：145的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW-7 antigens can elicit antibodies that recognize SEQ ID NO: 145 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 145 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 145, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These NW_7 proteins include variants of SEQ ID NO:145. A preferred fragment of (b) comprises an epitope from SEQ ID NO:145. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 145 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 145, and At least one epitope of SEQ ID NO: 145 is retained. The first 17 N-terminal amino acids of SEQ ID NO: 145 can be usefully omitted. Other fragments omit one or more protein domains.

NW_8NW_8

“NW_8”抗原注释为“趋化作用抑制蛋白CHIPS”。在Newman菌株中，NW_8是NWMN_1877，具有氨基酸序列SEQ ID NO：146(GI：151222089)。The "NW_8" antigen is annotated as "Chemotaxis Inhibitor Protein CHIPS". In the Newman strain, NW_8 is NWMN_1877, having the amino acid sequence of SEQ ID NO: 146 (GI: 151222089).

有用的NW_8抗原能引发识别SEQ ID NO：146的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：146有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：146的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100或更高)。这些NW_8蛋白包括SEQ ID NO：146的变体。(b)的优选片段包含来自SEQ ID NO：146的表位。其它优选片段缺少SEQ IDNO：146的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：146的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：146的至少一个表位。SEQ ID NO：146的前19个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_8 antigens can elicit antibodies that recognize SEQ ID NO: 146 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 146 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 146, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100 or higher). These NW_8 proteins include variants of SEQ ID NO:146. A preferred fragment of (b) comprises an epitope from SEQ ID NO:146. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 146 and / or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminal of SEQ ID NO: 146, and At least one epitope of SEQ ID NO: 146 is retained. The first 19 N-terminal amino acids of SEQ ID NO: 146 can be usefully omitted. Other fragments omit one or more protein domains.

NW_2NW_2

“NW_2”抗原注释为“内毒素A型前体”。在Newman菌株中，NW_2是NWMN_1883，具有氨基酸序列SEQ ID NO：147(GI：151222095)。The "NW_2" antigen is annotated as "endotoxin type A precursor". In the Newman strain, NW_2 is NWMN_1883, having the amino acid sequence of SEQ ID NO: 147 (GI: 151222095).

有用的NW_2抗原能引发识别SEQ ID NO：147的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：147有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：147的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些NW_2蛋白包括SEQ ID NO：147的变体。(b)的优选片段包含来自SEQ ID NO：147的表位。其它优选片段缺少SEQ ID NO：147的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：147的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：147的至少一个表位。SEQ ID NO：147的前16个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_2 antigens can elicit antibodies that recognize SEQ ID NO: 147 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 147 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 147, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These NW_2 proteins include variants of SEQ ID NO:147. A preferred fragment of (b) comprises an epitope from SEQ ID NO:147. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 147 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 147, while retaining at least one epitope of SEQ ID NO: 147. The first 16 N-terminal amino acids of SEQ ID NO: 147 can be usefully omitted. Other fragments omit one or more protein domains.

NW_1NW_1

“NW_1”抗原注释为“脂蛋白”。在Newman菌株中，NW_1是NWMN_1924，具有氨基酸序列SEQ ID NO：148(GI：151222136)。The "NW_1" antigen is annotated as "lipoprotein". In the Newman strain, NW_1 is NWMN_1924, having the amino acid sequence of SEQ ID NO: 148 (GI: 151222136).

有用的NW_1抗原能引发识别SEQ ID NO：148的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：148有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：148的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150或更高)。这些NW_1蛋白包括SEQ ID NO：148的变体。(b)的优选片段包含来自SEQ ID NO：148的表位。其它优选片段缺少SEQ ID NO：148的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：148的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：148的至少一个表位。SEQ ID NO：148的前17个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_1 antigens can elicit antibodies that recognize SEQ ID NO: 148 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 148 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 148, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or higher). These NW_1 proteins include variants of SEQ ID NO:148. A preferred fragment of (b) comprises an epitope from SEQ ID NO:148. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 148 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 148, While retaining at least one epitope of SEQ ID NO: 148. The first 17 N-terminal amino acids of SEQ ID NO: 148 can be usefully omitted. Other fragments omit one or more protein domains.

NW_5NW_5

“NW_5”抗原注释为“细胞壁表面锚定家族蛋白”。在Newman菌株中，NW_5是NWMN_2392，具有氨基酸序列SEQ ID NO：149(GI：151222604)。"NW_5" antigen is annotated as "cell wall surface anchor family protein". In the Newman strain, NW_5 is NWMN_2392, having the amino acid sequence of SEQ ID NO: 149 (GI: 151222604).

有用的NW_5抗原能引发识别SEQ ID NO：149的抗体(例如，给予人时)和/或可包含某种氨基酸序列，所述氨基酸序列：(a)与SEQ ID NO：149有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：149的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。这些NW_5蛋白包括SEQ ID NO：149的变体。(b)的优选片段包含来自SEQ ID NO：149的表位。其它优选片段缺少SEQ ID NO：149的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：149的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：149的至少一个表位。SEQ ID NO：149的前52个N-末端氨基酸可有用地省去。其它片段省去一个或多个蛋白质结构域。Useful NW_5 antigens can elicit antibodies that recognize SEQ ID NO: 149 (e.g., when administered to a human) and/or can comprise an amino acid sequence that: (a) is 50% or more identical to SEQ ID NO: 149 High identity (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% , 99%, 99.5% or higher); and/or (b) a fragment comprising at least 'n' contiguous amino acids of SEQ ID NO: 149, wherein 'n' is 7 or higher (e.g. 8, 10, 12 , 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or higher). These NW_5 proteins include variants of SEQ ID NO:149. A preferred fragment of (b) comprises an epitope from SEQ ID NO:149. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the C-terminus of SEQ ID NO: 149 and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) of the N-terminus of SEQ ID NO: 149, While retaining at least one epitope of SEQ ID NO: 149. The first 52 N-terminal amino acids of SEQ ID NO: 149 can be usefully omitted. Other fragments omit one or more protein domains.

杂交多肽hybrid peptide

本发明所用的抗原可作为分离的各多肽存在于组合物中。然而，如果使用多于一种抗原，它们不一定作为分离的多肽存在。取而代之的是，至少两种(如2、3、4、5或更多种)抗原反而可表达成一条多肽链(‘杂交’多肽)。杂交多肽提供两个主要优点：首先，本身不稳定或者表达较差的多肽可通过加入能克服该问题的合适杂交伴侣而得到改善；其次，商业生产得以简化，因为只需利用一次表达和纯化以生产可用作抗原的两种多肽。The antigens used in the present invention may be present in the composition as separate individual polypeptides. However, if more than one antigen is used, they do not necessarily exist as isolated polypeptides. Instead, at least two (eg 2, 3, 4, 5 or more) antigens may instead be expressed as one polypeptide chain ('hybrid' polypeptide). Hybrid peptides offer two major advantages: first, peptides that are inherently unstable or poorly expressed can be improved by adding suitable hybrid partners that overcome this problem; second, commercial production is simplified because only one expression and purification Two polypeptides are produced that can be used as antigens.

杂交多肽可包含来自第一抗原组的两种或更多种多肽序列。杂交多肽可包含来自第一抗原组的一种或多种多肽序列，和来自第二抗原组的一种或多种多肽序列。此外，杂交多肽可包含来自上述各抗原的两种或更多种多肽序列，或在该序列在菌株间有部分变化的情况下，可包含相同抗原的两种或更多种变体。A hybrid polypeptide may comprise two or more polypeptide sequences from a first group of antigens. A hybrid polypeptide may comprise one or more polypeptide sequences from a first antigenic group, and one or more polypeptide sequences from a second antigenic group. Furthermore, hybrid polypeptides may comprise two or more polypeptide sequences from each of the above antigens, or, where the sequences partially vary between strains, may comprise two or more variants of the same antigen.

可使用由两种、三种、四种、五种、六种、七种、八种、九种或十种抗原的氨基酸序列组成的杂交体。具体说，优选由两种、三种、四种或五种抗原，如两种或三种抗原的氨基酸序列组成的杂交体。Hybrids consisting of the amino acid sequences of two, three, four, five, six, seven, eight, nine or ten antigens may be used. In particular, hybrids consisting of two, three, four or five antigens, such as amino acid sequences of two or three antigens, are preferred.

不同的杂交多肽可以混合在一种制剂中。杂交体可与选自第一、第二或第三抗原组的非杂交抗原组合。在此类组合中，抗原可存在于多于一种的杂交多肽中和/或作为非杂交多肽存在。然而，抗原优选作为杂交体或作为非杂交体存在，但不同时存在两种形式。Different hybrid polypeptides can be mixed in one formulation. Hybrids may be combined with non-hybrid antigens selected from the first, second or third antigen group. In such combinations, the antigens may be present in more than one hybrid polypeptide and/or as non-hybrid polypeptides. However, the antigen is preferably present as a hybrid or as a non-hybrid, but not both.

杂交多肽也可与上述偶联物或非金黄色葡萄球菌抗原组合。Hybrid polypeptides may also be combined with the aforementioned conjugates or non-S. aureus antigens.

杂交多肽可以表示为通式NH2-A-{-X-L-}n-B-COOH，其中：X是金黄色葡萄球菌抗原的氨基酸序列，如上所述；L是任选接头的氨基酸序列；A是任选的N末端氨基酸序列；B是任选的C末端氨基酸序列；n是2或更大的整数(如2、3、4、5、6等)。n通常是2或3。The hybrid polypeptide can be represented by the general formula NH 2 -A-{-XL-} n -B-COOH, wherein: X is the amino acid sequence of Staphylococcus aureus antigen, as described above; L is the amino acid sequence of an optional linker; A is an optional N-terminal amino acid sequence; B is an optional C-terminal amino acid sequence; n is an integer of 2 or more (such as 2, 3, 4, 5, 6, etc.). n is usually 2 or 3.

如果在其野生型形式中-X-部分具有前导肽序列，则在杂交蛋白中可包含或者略去该序列。在一些实施方式中，前导肽可缺失，除非-X-部分位于杂交蛋白的N-末端，即保留X1的前导肽，但略去X2...Xn的前导肽。这相当于删除所有前导肽并使用X1的前导肽作为-A-部分。If the -X- portion has a leader peptide sequence in its wild-type form, this sequence can be included or omitted in the hybrid protein. In some embodiments, the leader peptide can be deleted unless the -X- moiety is located at the N-terminus of the hybrid protein, ie the leader peptide of X1 is retained, but the leader peptides of X2 ... Xn are omitted. This is equivalent to deleting all leader peptides and using the leader peptide of X1 as the -A- moiety.

对于{-X-L-}的各个n的情况下，接头氨基酸序列-L-可存在或不存在。例如，当n＝2时，杂交体可以是NH2-X1-L1-X2-L2-COOH、NH2-X1-X2-COOH、NH2-X1-L1-X2-COOH、NH2-X1-X2-L2-COOH等。接头氨基酸序列-L-一般较短(如20个或更少的氨基酸，即20、19、18、17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1)。例子包括有利于克隆的短肽序列，聚-甘氨酸接头(即包含Glyn，其中n＝2、3、4、5、6、7、8、9、10或更高)，和组氨酸标签(即Hisn，其中n＝3、4、5、6、7、8、9、10或更高)。本领域技术人员了解其它合适的接头氨基酸序列。有用的接头是GSGGGG(SEQID NO：171)或GSGSGGGG(SEQ ID NO：172)，其中Gly-Ser二肽由BamHI限制性位点形成(或两个它们形成SEQ ID NO：230四肽)，因而有助于克隆和操作，而(Gly)4四肽(SEQ ID NO：227)是典型的多聚-甘氨酸接头。其它合适的接头是ASGGGS(SEQ ID NO：173，例如SEQ ID NO：174编码)或Leu-Glu二肽，尤其是对于用作最后的Ln。For each case of n of {-XL-}, the linker amino acid sequence -L- may or may not be present. For example, when n=2, the hybrid can be NH 2 -X 1 -L 1 -X 2 -L 2 -COOH, NH 2 -X 1 -X 2 -COOH, NH 2 -X 1 -L 1 -X 2 -COOH, NH 2 -X 1 -X 2 -L 2 -COOH, etc. The linker amino acid sequence -L- is generally shorter (e.g. 20 or fewer amino acids, i.e. 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples include short peptide sequences to facilitate cloning, poly-glycine linkers (i.e., containing Gly n , where n = 2, 3, 4, 5, 6, 7, 8, 9, 10 or higher), and histidine tags (ie His n , where n=3, 4, 5, 6, 7, 8, 9, 10 or higher). Other suitable linker amino acid sequences are known to those skilled in the art. Useful linkers are GSGGGG (SEQ ID NO: 171) or GSGSGGGG (SEQ ID NO: 172), where the Gly-Ser dipeptide is formed by the BamHI restriction site (or both of them form the SEQ ID NO: 230 tetrapeptide), thus Facilitating cloning and manipulation, and (Gly) 4 tetrapeptide (SEQ ID NO: 227) is a typical poly-glycine linker. Other suitable linkers are ASGGGS (SEQ ID NO: 173, eg encoded by SEQ ID NO: 174) or the Leu-Glu dipeptide, especially for use as the final Ln .

-A-是任选的N末端氨基酸序列。其一般较短(如40个或更少的氨基酸，即40、39、38、37、36、35、34、33、32、31、30、29、28、27、26、25、24、23、22、21、20、19、18、17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1个)。例子包括指导蛋白运输的前导序列，或有利于克隆或纯化的短肽序列(如组氨酸标签，即Hisn，其中n＝3、4、5、6、7、8、9、10或更多)。本领域技术人员知道其它合适的N-末端氨基酸序列。如果X1缺少其自身的N-末端甲硫氨酸，-A-优选是提供N-末端甲硫氨酸的寡肽(例如，具有1、2、3、4、5、6、7或8个氨基酸)，如Met-Ala-Ser或单个Met残基。-A- is an optional N-terminal amino acid sequence. It is generally shorter (such as 40 or fewer amino acids, i.e. 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23 , 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples include leader sequences that direct protein trafficking, or short peptide sequences that facilitate cloning or purification (such as histidine tags, i.e. His n , where n = 3, 4, 5, 6, 7, 8, 9, 10 or more many). Other suitable N-terminal amino acid sequences are known to those skilled in the art. If X lacks its own N-terminal methionine, -A- is preferably an oligopeptide providing an N-terminal methionine (e.g., with 1, 2, 3, 4, 5, 6, 7 or 8 amino acids), such as Met-Ala-Ser or a single Met residue.

-B-是任选的C末端氨基酸序列。其一般较短(如40个或更少的氨基酸，即39、38、37、36、35、34、33、32、31、30、29、28、27、26、25、24、23、22、21、20、19、18、17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1个)。例子包括指导蛋白质运输的序列，有利于克隆或纯化的短肽序列(如包含组氨酸标签，即Hisn，其中n＝3、4、5、6、7、8、9、10或更多，例如SEQ ID NO：226)，或能提高蛋白质稳定性的序列。本领域技术人员知道其它合适的C末端氨基酸序列。-B- is an optional C-terminal amino acid sequence. It is generally shorter (such as 40 or fewer amino acids, i.e. 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22 , 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples include sequences that direct protein trafficking, short peptide sequences that facilitate cloning or purification (such as those containing a histidine tag, i.e. His n , where n = 3, 4, 5, 6, 7, 8, 9, 10 or more , such as SEQ ID NO: 226), or sequences that increase protein stability. Other suitable C-terminal amino acid sequences are known to those skilled in the art.

本发明的一种杂交多肽可包含EsxA和EsxB抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：151(‘EsxAB’；SEQ ID NO：169编码)和152(‘EsxBA’)是此类杂交体的例子，二者均具有六肽接头ASGGGS(SEQID NO：173)。另一种‘EsxAB’杂交体包含SEQ ID NO：241，提供N-末端甲硫氨酸(例如，SEQ ID NO：250)。A hybrid polypeptide of the invention may comprise EsxA and EsxB antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 151 ('EsxAB'; encoded by SEQ ID NO: 169) and 152 ('EsxBA') are examples of such hybrids, both of which have the hexapeptide linker ASGGGS (SEQ ID NO: 173). Another 'EsxAB' hybrid comprises SEQ ID NO: 241, providing an N-terminal methionine (e.g., SEQ ID NO: 250).

本发明的另一种杂交多肽可包含SdrD和SdrE抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：168(‘SdrED’)是此类杂交体的实例，具有六肽接头ASGGGS(SEQ ID NO：173)。Another hybrid polypeptide of the invention may comprise SdrD and SdrE antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 168 ('SdrED') is an example of such a hybrid, with the hexapeptide linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可同时包含ClfB和SdrD抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：202(‘ClfB-SdrD’)是此类杂交体的实例，具有六肽接头ASGGGS(SEQ ID NO：173)。SEQ ID NO：203(‘SdrD-ClfB’)是此类杂交体的另一实例，具有六肽接头ASGGGS(SEQ IDNO：173)。SEQ ID NO：211(‘ClfB-N3-sdrD-N3’)是此类杂交体的另一实例，其中ClfB和SdrD由六肽接头ASGGGS(SEQ ID NO：173)连接。Another hybrid polypeptide of the present invention may contain both CIfB and SdrD antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 202 ('CIfB-SdrD') is an example of such a hybrid, with the hexapeptide linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 203 ('SdrD-ClfB') is another example of such a hybrid, with the hexapeptide linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 211 ('CIfB-N3-sdrD-N3') is another example of such a hybrid, wherein CIfB and SdrD are linked by a hexapeptide linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可同时包含IsdA和EsxA抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：204(‘IsdA-EsxA’)是此类杂交体的实例，具有六肽接头ASGGGS(SEQ ID NO：173)。SEQ ID NO：209(‘isdA40-184-esxA’)是此类杂交体的另一实例，其中IsdA40-184由接头ASGGGS(SEQ ID NO：173)连接于EsxA。Another hybrid polypeptide of the invention may contain both IsdA and EsxA antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 204 ('IsdA-EsxA') is an example of such a hybrid, with the hexapeptide linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 209 ('isdA40-184-esxA') is another example of such a hybrid, wherein IsdA 40-184 is linked to EsxA by a linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可同时包含IsdA和sta006抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：221(‘isdA40-184-sta006’)是此类杂交体的实例，其中IsdA40-184由接头ASGGGS(SEQ ID NO：173)连接于Sta006。Another hybrid polypeptide of the present invention may contain both IsdA and sta006 antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 221 ('isdA40-184-sta006') is an example of such a hybrid, wherein IsdA 40-184 is linked to Sta006 by a linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可同时包含Hla和sta006抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：222(‘HlaH35L-sta006’)是此类杂交体的实例，其中Hla的H35L突变体由六肽接头ASGGGS(SEQ ID NO：173)连接于Sta006。Another hybrid polypeptide of the present invention may contain both Hla and sta006 antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 222 ('HlaH35L-sta006') is an example of such a hybrid, wherein the H35L mutant of Hla is linked to Sta006 by a hexapeptide linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可同时包含Hla和Emp抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：205(‘HlaH35L-Emp’)是此类杂交体的实例，其中H35L突变体Hla由接头ASGGGS(SEQ ID NO：173)连接于Emp。SEQ ID NO：206(‘Hla27-76-Emp’)是此类杂交体的另一实例，其中Hla片段由接头ASGGGS(SEQ ID NO：173)连接于Emp；SEQ ID NO：207是SEQ ID NO：206的H35L突变体。SEQ ID NO：208(‘HlaPSGS-Emp’)是此类杂交体的另一实例，其中Hla突变体由接头ASGGGS(SEQ ID NO：173)连接于Emp。Another hybrid polypeptide of the present invention may contain both Hla and Emp antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 205 ('HlaH35L-Emp') is an example of such a hybrid, wherein the H35L mutant Hla is joined to Emp by a linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 206 ('Hla27-76-Emp') is another example of such a hybrid, wherein the Hla fragment is joined to Emp by a linker ASGGGS (SEQ ID NO: 173); SEQ ID NO: 207 is SEQ ID NO :206 of the H35L mutant. SEQ ID NO: 208 ('HlaPSGS-Emp') is another example of such a hybrid, wherein the Hla mutant is joined to Emp by a linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可包含IsdA和EsxA及EsxB抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：210(‘isdA40-184-esxAB’)是此类杂交体的实例，其中IsdA40-184由接头ASGGGS(SEQ ID NO：173)连接于EsxAB。EsxAB已包含相同的接头，因此SEQ ID NO：210包含两个这样的接头。SEQ ID NO：212(‘IsdA-esxAB’)是此类三联杂交体的另一实例，其中IsdA由接头ASGGGS(SEQ ID NO：173)连接于EsxAB。Another hybrid polypeptide of the invention may comprise IsdA and EsxA and EsxB antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 210 ('isdA40-184-esxAB') is an example of such a hybrid, wherein IsdA 40-184 is linked to EsxAB by a linker ASGGGS (SEQ ID NO: 173). EsxAB already contains the same linker, so SEQ ID NO: 210 contains two such linkers. SEQ ID NO: 212 ('IsdA-esxAB') is another example of such a triple hybrid, wherein IsdA is linked to EsxAB by a linker ASGGGS (SEQ ID NO: 173).

本发明的另一种杂交多肽可包含Hla和EsxA及EsxB抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：220(‘HlaH35L-esxAB’)是此类三联杂交体的实例，其中Hla的H35L突变体由接头ASGGGS(SEQ IDNO：173)连接于EsxAB。EsxAB已包含相同的接头，因此SEQ ID NO：220包含两个这样的接头。包含Hla和EsxA及EsxB抗原的杂交多肽的另一实例是SEQ ID NO：237(如实施例中使用的‘HlaH35L-esxAB’)，其中Hla的H35L突变体由接头APTARG(SEQ ID NO：239)连接于EsxA以替代其N-末端，然后由接头ASGGGS(SEQ ID NO：173)连接于EsxB以替代其N-末端。该杂交体可提供合适的N-末端序列，例如SEQ ID NO：240。Another hybrid polypeptide of the invention may comprise Hla and EsxA and EsxB antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 220 ('HlaH35L-esxAB') is an example of such a triple hybrid, wherein the H35L mutant of Hla is linked to EsxAB by a linker ASGGGS (SEQ ID NO: 173). EsxAB already contains the same linker, so SEQ ID NO: 220 contains two such linkers. Another example of a hybrid polypeptide comprising Hla and EsxA and EsxB antigens is SEQ ID NO: 237 ('HlaH35L-esxAB' as used in the Examples), wherein the H35L mutant of Hla is linked by the linker APTARG (SEQ ID NO: 239) Linked to EsxA to replace its N-terminus, and then connected to EsxB by linker ASGGGS (SEQ ID NO: 173) to replace its N-terminus. The hybrid can provide a suitable N-terminal sequence, such as SEQ ID NO:240.

本发明的另一种杂交多肽可包含sta006和EsxA及EsxB抗原。从N-到C-末端，这些抗原可采用任一顺序。SEQ ID NO：223(‘sta006-esxAB’)是此类三联杂交体的实例，其中sta006由接头ASGGGS(SEQ ID NO：173)连接于EsxAB。EsxAB已包含相同的接头，因此SEQ ID NO：223包含两个这样的接头。包含sta006和EsxA及EsxB抗原的杂交多肽的另一实例是SEQID NO：238(如实施例中使用的‘sta006-esxAB’)，其中sta006由接头APTARG(SEQ ID NO：239)连接于EsxA以替代其N-末端，然后由接头ASGGGS(SEQID NO：173)连接于EsxB以替代其N-末端。该杂交体可提供合适的N-末端序列，例如SEQ ID NO：240。Another hybrid polypeptide of the invention may comprise sta006 and the EsxA and EsxB antigens. These antigens may be in any order from N- to C-terminus. SEQ ID NO: 223 ('sta006-esxAB') is an example of such a triple hybrid, wherein sta006 is linked to EsxAB by a linker ASGGGS (SEQ ID NO: 173). EsxAB already contains the same linker, so SEQ ID NO: 223 contains two such linkers. Another example of a hybrid polypeptide comprising sta006 and EsxA and EsxB antigens is SEQ ID NO: 238 ('sta006-esxAB' as used in the Examples), wherein sta006 is linked to EsxA by a linker APTARG (SEQ ID NO: 239) in place of Its N-terminus was then ligated to EsxB by the linker ASGGGS (SEQ ID NO: 173) to replace its N-terminus. The hybrid can provide a suitable N-terminal sequence, such as SEQ ID NO:240.

通常，这些杂交多肽能有用地引发识别该杂交体中所含各野生型葡萄球菌蛋白(例如，序列表所示)的抗体(例如，给予人时)，例如同时识别野生型EsxA和野生型EsxB，或同时识别野生型SdrD和野生型SdrE，或同时识别野生型SdrD和野生型ClfB，或同时识别野生型IsdA和野生型EsxA，或同时识别野生型IsdA和野生型sta006，或同时识别野生型Hla和野生型sta006，或同时识别野生型Hla和野生型Emp，或识别野生型IsdA和野生型EsxA及野生型EsxB，或识别野生型Hla和野生型EsxA及野生型EsxB，或识别野生型sta006和野生型EsxA及野生型EsxB。Typically, these hybrid polypeptides are useful for eliciting antibodies (e.g., when administered to a human) that recognize each of the wild-type staphylococcal proteins (e.g., as shown in the Sequence Listing) contained in the hybrid, e.g., both wild-type EsxA and wild-type EsxB , or both wild-type SdrD and wild-type SdrE, or both wild-type SdrD and wild-type ClfB, or both wild-type IsdA and wild-type EsxA, or both wild-type IsdA and wild-type sta006, or both wild-type Hla and wild-type sta006, or recognize wild-type Hla and wild-type Emp at the same time, or recognize wild-type IsdA and wild-type EsxA and wild-type EsxB, or recognize wild-type Hla and wild-type EsxA and wild-type EsxB, or recognize wild-type sta006 and wild-type EsxA and wild-type EsxB.

本发明所用多肽Polypeptides used in the present invention

本发明所用多肽可采取各种形式(如天然多肽、融合多肽、糖基化多肽、非糖基化多肽、脂化多肽、非脂化多肽、磷酸化多肽、非磷酸化多肽、肉豆蔻酰化多肽、非肉豆蔻酰化多肽、单体、多聚体、颗粒、变性多肽等)。The polypeptides used in the present invention can take various forms (e.g., native polypeptides, fusion polypeptides, glycosylated polypeptides, non-glycosylated polypeptides, lipidated polypeptides, non-lipidated polypeptides, phosphorylated polypeptides, non-phosphorylated polypeptides, myristoylated peptides, non-myristoylated peptides, monomers, polymers, particles, denatured peptides, etc.).

本发明所用多肽可通过各种方式(如重组表达、由细胞培养物纯化、化学合成等)制备。优选重组表达的蛋白质，特别是杂交多肽。The polypeptides used in the present invention can be prepared in various ways (such as recombinant expression, purification from cell culture, chemical synthesis, etc.). Recombinantly expressed proteins are preferred, especially hybrid polypeptides.

本发明所用多肽优选以纯化或基本纯化的形式，即，基本不含其它多肽(如不含天然产生的多肽)、特别是不含其它葡萄球菌或宿主细胞多肽的形式提供，其纯度通常为至少约50重量％，通常至少约90％，即，组成中少于约50％，更优选少于约10％(如5％)由其它表达的多肽构成。因此，组合物中的抗原是与表达该分子的完整生物体分离的。The polypeptides used in the present invention are preferably provided in a purified or substantially purified form, i.e., substantially free of other polypeptides (eg, free of naturally occurring polypeptides), especially free of other staphylococcal or host cell polypeptides, usually at a purity of at least About 50% by weight, usually at least about 90%, ie, less than about 50%, more preferably less than about 10% (eg, 5%) of the composition consists of other expressed polypeptides. Thus, the antigen in the composition is isolated from the whole organism expressing the molecule.

本发明所用多肽优选葡萄球菌多肽。The polypeptides used in the present invention are preferably staphylococcal polypeptides.

术语“多肽”指任何长度的氨基酸聚合物。该聚合物可以是线性或支化聚合物，可包含修饰的氨基酸，可且可被非氨基酸中断。该术语也包括经天然或通过人工介入修饰的氨基酸聚合物；例如，二硫键形成、糖基化、脂化、乙酰化、磷酸化或任何其它操作或修饰，如与标记组分偶联。该定义还包括(例如)含有一个或多个氨基酸类似物(包括例如，非天然氨基酸等)以及本领域已知的其它修饰的多肽。多肽可以以单链或结合链的形式产生。The term "polypeptide" refers to a polymer of amino acids of any length. The polymer may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acids. The term also includes amino acid polymers that have been modified, either naturally or by human intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within this definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. Polypeptides can be produced as single chains or as associated chains.

本发明提供含有序列-P-Q-或-Q-P-的多肽，其中：-P-是上述氨基酸序列，-Q-不是上述序列，即，本发明提供融合蛋白。如果-P-的N-末端密码子不是ATG，但该密码子未存在于多肽的N末端，它被翻译成该密码子的标准氨基酸，而非Met。然而，如果该密码子位于多肽的N末端，它被翻译成Met。-Q-部分的例子包括但不限于：组氨酸标签(即Hisn，其中n＝3、4、5、6、7、8、9、10或更高)、麦芽糖结合蛋白或谷胱甘肽-S-转移酶(GST)。The present invention provides a polypeptide containing the sequence -PQ- or -QP-, wherein: -P- is the above-mentioned amino acid sequence, and -Q- is not the above-mentioned sequence, that is, the present invention provides a fusion protein. If the N-terminal codon of -P- is not ATG, but this codon is not present at the N-terminus of the polypeptide, it is translated to the standard amino acid for that codon, not Met. However, if the codon is located at the N-terminus of the polypeptide, it is translated into Met. Examples of -Q- moieties include, but are not limited to: histidine tag (ie His n , where n = 3, 4, 5, 6, 7, 8, 9, 10 or higher), maltose binding protein or glutathione Peptide-S-transferase (GST).

本发明还提供产生本发明多肽的方法，包括在诱导多肽表达的条件下培养用本发明核酸转化的宿主细胞的步骤。The present invention also provides a method for producing a polypeptide of the present invention, comprising the step of culturing a host cell transformed with a nucleic acid of the present invention under conditions that induce expression of the polypeptide.

虽然可以在葡萄球菌中表达本发明多肽，但通常使用异源宿主以供表达(重组表达)。异源宿主可以是原核(例如细菌)或真核生物。宿主可以是大肠杆菌(E.coli)，但其他合适的宿主包括枯草芽孢杆菌(Bacillus subtilis)、霍乱弧菌(Vibrio cholerae)、伤寒沙门菌(Salmonella typhi)、鼠伤寒沙门菌(Salmonella typhimurium)、乳酰胺奈瑟菌(Neisseria lactamica)、灰色奈瑟菌(Neisseria cinerea)、分枝杆菌(Mycobacteria)(例如结核分支杆菌(M.tuberculosis))、酵母等。与编码本发明多肽的野生型金黄色葡萄球菌基因相比，优选改变密码子以优化在此类宿主中的表达效率而不影响编码的氨基酸。Although it is possible to express the polypeptides of the invention in staphylococci, typically a heterologous host is used for expression (recombinant expression). A heterologous host can be prokaryotic (eg, bacteria) or eukaryotic. The host can be E. coli, but other suitable hosts include Bacillus subtilis, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Neisseria lactamica, Neisseria cinerea, Mycobacteria (eg M. tuberculosis), yeast, etc. Compared to wild-type S. aureus genes encoding polypeptides of the invention, codons are preferably altered to optimize expression efficiency in such hosts without affecting the encoded amino acids.

本发明提供产生本发明多肽的方法，包括通过化学方式合成所述多肽的至少一部分的步骤。The invention provides a method of producing a polypeptide of the invention comprising the step of chemically synthesizing at least a portion of said polypeptide.

核酸nucleic acid

本发明也提供编码本发明多肽和杂交多肽的核酸。还提供包含编码一种或多种本发明多肽或杂交多肽的核苷酸序列的核酸。The invention also provides nucleic acids encoding polypeptides and hybrid polypeptides of the invention. Nucleic acids comprising nucleotide sequences encoding one or more polypeptides or hybrid polypeptides of the invention are also provided.

本发明还提供所含的核苷酸序列与此类核苷酸序列有序列相同性的核酸。序列之间的相同性优选通过Smith-Waterman同源性检索算法(如上所述)确定。此类核酸包括使用替代密码子编码同一氨基酸的核酸。The invention also provides nucleic acids comprising nucleotide sequences having sequence identity to such nucleotide sequences. Identity between sequences is preferably determined by the Smith-Waterman homology search algorithm (described above). Such nucleic acids include nucleic acids that encode the same amino acid using alternative codons.

本发明还提供可与这些核酸杂交的核酸。可以在不同“严谨性”条件下进行杂交反应。提高杂交反应严谨性的条件是本领域熟知的，且已公开过[如参考文献276的第7.52页]。相关条件的例子包括(按严谨性提高的顺序)：温育温度25℃、37℃、50℃、55℃和68℃；缓冲液浓度10x SSC、6x SSC、1x SSC、0.1x SSC(其中SSC是0.15M NaCl和15mM柠檬酸盐缓冲液)和使用其它缓冲液体系的等同条件；甲酰胺浓度0％、25％、50％和75％；温育时间5分钟到24小时；1个、2个或多个洗涤步骤；洗涤温育时间1、2或15分钟；洗涤溶液6x SSC、1x SSC、0.1x SSC或去离子水。杂交技术和其优化方法是本领域熟知的[例如，参见参考文献75、76、276、278等]。The present invention also provides nucleic acids that can hybridize to these nucleic acids. Hybridization reactions can be performed under conditions of varying "stringency". Conditions that increase the stringency of hybridization reactions are well known in the art and have been published [eg, p. 7.52 of ref. 276]. Examples of relevant conditions include (in order of increasing stringency): incubation temperature 25°C, 37°C, 50°C, 55°C, and 68°C; buffer concentration 10x SSC, 6x SSC, 1x SSC, 0.1x SSC (where SSC 0.15M NaCl and 15mM citrate buffer) and equivalent conditions using other buffer systems; formamide concentration 0%, 25%, 50% and 75%; incubation time 5 minutes to 24 hours; 1, 2 One or more wash steps; wash incubation time 1, 2 or 15 minutes; wash solution 6x SSC, 1x SSC, 0.1x SSC or deionized water. Hybridization techniques and methods for their optimization are well known in the art [eg, see references 75, 76, 276, 278, etc.].

在一些实施方式中，本发明核酸与靶标在低严谨条件下杂交；在其它实施方式中，在中等严谨条件下杂交；在优选实施方式中，在高严谨条件下杂交。一组示范性的低严谨杂交条件是50℃和10x SSC。一组示范性的中等严谨杂交条件是55℃和1x SSC。一组示范性的高严谨杂交条件是68℃和0.1x SSC。In some embodiments, a nucleic acid of the invention hybridizes to a target under conditions of low stringency; in other embodiments, under conditions of moderate stringency; and in preferred embodiments, under conditions of high stringency. An exemplary set of low stringency hybridization conditions is 50°C and 10x SSC. An exemplary set of moderately stringent hybridization conditions is 55°C and 1x SSC. An exemplary set of highly stringent hybridization conditions is 68°C and 0.1x SSC.

本发明包括含有这些序列的互补序列的核酸(例如，用作反义链或探针，或用作引物)。The invention includes nucleic acids comprising the complements of these sequences (eg, for use as antisense strands or probes, or as primers).

本发明核酸可用于杂交反应(如Northern或Southern印迹，或用于核酸微阵列或‘基因芯片’)和扩增反应(如PCR、SDA、SSSR、LCR、TMA、NASBA等)和其它核酸技术。The nucleic acids of the invention can be used in hybridization reactions (such as Northern or Southern blots, or in nucleic acid microarrays or 'gene chips') and amplification reactions (such as PCR, SDA, SSSR, LCR, TMA, NASBA, etc.) and other nucleic acid techniques.

本发明核酸可采取各种形式(如单链、双链、载体、引物、探针、标记形式等)。本发明核酸可以是环状或分支状核酸，但通常是线性核酸。除非另有说明或要求，利用核酸的本发明任何实施方式可利用双链形式和构成该双链形式的两条互补单链形式的各链。引物和探针通常是单链的，反义核酸亦然。Nucleic acids of the invention can take various forms (eg, single-stranded, double-stranded, vector, primer, probe, labeled form, etc.). Nucleic acids of the invention may be circular or branched, but are typically linear. Unless otherwise stated or required, any embodiment of the invention utilizing a nucleic acid may utilize a double-stranded form and each strand of the two complementary single-stranded forms that make up the double-stranded form. Primers and probes are usually single-stranded, as are antisense nucleic acids.

本发明核酸优选以纯化或基本纯化的形式提供，即，基本不含其它核酸(如不含天然产生的核酸)，特别是不含其它葡萄球菌或宿主细胞核酸，通常其纯度至少为约50重量％，通常至少为约90％。本发明核酸优选为葡萄球菌核酸。Nucleic acids of the invention are preferably provided in purified or substantially purified form, i.e., substantially free of other nucleic acids (e.g., free of naturally occurring nucleic acids), especially free of other staphylococcal or host cell nucleic acids, usually at a purity of at least about 50 wt. %, usually at least about 90%. The nucleic acid of the invention is preferably a staphylococcal nucleic acid.

可以多种方式制备本发明的核酸，例如，完全或部分化学合成(例如DNA的亚磷酰胺合成)、利用核酸酶(例如限制性酶)消化较长核酸、连接较短核酸或核苷酸(例如使用连接酶或聚合酶)、由基因组或cDNA文库制备等。Nucleic acids of the invention can be prepared in a variety of ways, for example, by complete or partial chemical synthesis (e.g., phosphoramidite synthesis of DNA), digestion of longer nucleic acids with nucleases (e.g., restriction enzymes), ligation of shorter nucleic acids or nucleotides ( For example using ligase or polymerase), preparation from genomic or cDNA library, etc.

本发明核酸可连接于固相载体(如珠、平板、滤纸、膜、载玻片、微阵列载体、树脂等)。可用，例如放射性或荧光标记物、或生物素标记物标记本发明核酸。如果要将核酸用于检测技术，例如核酸是引物或作为探针时，这特别有用。The nucleic acid of the present invention can be attached to a solid phase support (such as beads, plates, filter papers, membranes, glass slides, microarray supports, resins, etc.). Nucleic acids of the invention may be labeled with, for example, radioactive or fluorescent labels, or biotin labels. This is particularly useful if the nucleic acid is to be used in a detection technique, eg as a primer or as a probe.

术语“核酸”通常包括任何长度的聚合形式核苷酸，包含脱氧核糖核苷酸、核糖核苷酸和/或其类似物。它包括DNA、RNA、DNA/RNA杂交体。它还包括DNA或RNA类似物，如含有修饰主链(如肽核酸(PNA)或硫代磷酸酯)或修饰碱基的类似物。因此，本发明包括mRNA、tRNA、rRNA、核酶、DNA、cDNA、重组核酸、分支核酸、质粒、载体、探针、引物等。如果本发明核酸采取RNA形式，它可能具有或不具有5′帽。The term "nucleic acid" generally includes polymeric forms of nucleotides of any length, including deoxyribonucleotides, ribonucleotides, and/or analogs thereof. It includes DNA, RNA, DNA/RNA hybrids. It also includes analogs of DNA or RNA, such as those containing modified backbones (such as peptide nucleic acid (PNA) or phosphorothioate) or modified bases. Thus, the invention includes mRNA, tRNA, rRNA, ribozymes, DNA, cDNA, recombinant nucleic acids, branched nucleic acids, plasmids, vectors, probes, primers, and the like. If the nucleic acid of the invention is in the form of RNA, it may or may not have a 5' cap.

本发明核酸可以是载体的一部分，即，设计用于转导/转染一种或多种细胞类型的核酸构建物的一部分。载体可以是，例如，设计用于分离、增殖和复制插入的核苷酸的“克隆载体”，设计用于在宿主细胞中表达核苷酸序列的“表达载体”，设计用于产生重组病毒或病毒样颗粒的“病毒载体”，或具有一种以上载体类型的属性的“穿梭载体”。优选的载体是质粒。“宿主细胞”包括单个细胞或细胞培养物，它可能是或已经是外源核酸的接受者。宿主细胞包括单个宿主细胞的后代，由于天然、偶发或有意的突变和/或改变，这些后代与原始亲本细胞不一定完全相同(形态或总DNA互补方面)。宿主细胞包括用本发明核酸在体内或体外转染或感染的细胞。A nucleic acid of the invention may be part of a vector, ie part of a nucleic acid construct designed to transduce/transfect one or more cell types. Vectors may be, for example, "cloning vectors" designed for isolating, propagating and replicating inserted nucleotides, "expression vectors" designed for expression of nucleotide sequences in host cells, designed for the production of recombinant viruses or "Viral vectors" of virus-like particles, or "shuttle vectors" with properties of more than one vector type. Preferred vectors are plasmids. A "host cell" includes a single cell or cell culture that may be or has been a recipient of exogenous nucleic acid. Host cells include progeny of a single host cell which are not necessarily identical (in terms of morphology or total DNA complementation) to the original parent cell due to natural, accidental or deliberate mutations and/or alterations. Host cells include cells transfected or infected with nucleic acids of the invention in vivo or in vitro.

应理解，如果核酸是DNA，RNA序列中的“U”被DNA中的“T”所替代。相似地，应该知道如果核酸是RNA，DNA中的“T”被RNA序列中的“U”所替代。It is understood that if the nucleic acid is DNA, a "U" in the RNA sequence is replaced by a "T" in DNA. Similarly, it will be understood that if the nucleic acid is RNA, the "T" in DNA is replaced by a "U" in the RNA sequence.

涉及核酸的术语“互补”或“互补的”指沃森克里克(Watson-Crick)碱基配对。因此，与C互补的是G，与G互补的是C，与A互补的是T(或U)，与T(或U)互补的是A。还可能利用诸如I(嘌呤肌苷)等碱基，例如以便与嘧啶(C或T)互补。The terms "complementary" or "complementary" in reference to nucleic acids refer to Watson-Crick base pairing. Thus, the complement of C is G, the complement of G is C, the complement of A is T (or U), and the complement of T (or U) is A. It is also possible to use bases such as I (purine inosine), eg to be complementary to pyrimidines (C or T).

可利用本发明核酸，例如产生多肽；作为检测生物样品中核酸的杂交探针；产生额外的核酸拷贝；产生核酶或反义寡核苷酸；作为单链DNA引物或探针；或作为形成三链的寡核苷酸。Nucleic acids of the invention can be utilized, for example, to produce polypeptides; as hybridization probes for the detection of nucleic acids in biological samples; to produce additional copies of nucleic acids; to produce ribozymes or antisense oligonucleotides; as single-stranded DNA primers or probes; Triple-stranded oligonucleotides.

本发明提供产生本发明核酸的方法，其中所述核酸部分或完全用化学方式合成。The invention provides methods of producing nucleic acids of the invention wherein the nucleic acids are partially or fully chemically synthesized.

本发明提供包含本发明核苷酸序列的载体(如克隆或表达载体)和用此类载体转化的宿主细胞。The present invention provides vectors (such as cloning or expression vectors) comprising the nucleotide sequences of the present invention and host cells transformed with such vectors.

本发明核酸扩增可以是定量扩增和/或实时扩增。The nucleic acid amplification of the present invention may be quantitative amplification and/or real-time amplification.

对于本发明的某些实施方式，核酸的长度优选为至少7个核苷酸(如8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、45、50、55、60、65、70、75、80、90、100、110、120、130、140、150、160、170、180、190、200、225、250、275、300个核苷酸或更长)。For certain embodiments of the invention, the nucleic acid is preferably at least 7 nucleotides in length (e.g., 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300 nucleotides or longer).

对于本发明的某些实施方式，核酸长度优选至多为500个核苷酸(如450、400、350、300、250、200、150、140、130、120、110、100、90、80、75、70、65、60、55、50、45、40、39、38、37、36、35、34、33、32、31、30、29、28、27、26、25、24、23、22、21、20、19、18、17、16、15个核苷酸或更短)。For certain embodiments of the invention, the nucleic acid length is preferably at most 500 nucleotides (e.g., 450, 400, 350, 300, 250, 200, 150, 140, 130, 120, 110, 100, 90, 80, 75 , 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22 , 21, 20, 19, 18, 17, 16, 15 nucleotides or shorter).

本发明的引物和探针，以及用于杂交的其它核酸的长度优选为10-30个核苷酸(如10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30个核苷酸)。Primers and probes of the present invention, and other nucleic acids used for hybridization, are preferably 10-30 nucleotides in length (such as 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides).

菌株和变体Strains and variants

抗原的以上定义参考现有的命名(例如，“ClfA”)，“sta”编号或“NW_”编号。本文的表1将这三种命名/编号系统与现有的SAOUHSC编号和/或NWMN编号相关联。SAOUHSC编号指金黄色葡萄球菌菌株NCTC 8325的基因组(由俄克拉荷马大学卫生科学中心(Oklahoma University HealthSciences Center)测序，GenBank公开为CP000253.1；GI：87201381)，各SAOUHSC编号在基因组序列的“特征”部分给予“基因座_标签”条目。类似地，NWMN编号指金黄色葡萄球菌菌株Newman(1952年从人感染物中分离，具有稳定的毒力表型)的基因组，GenBank公开为AP009351.1(GI：150373012)，各NWMN编号在基因组序列的“特征”部分给予“基因座_标签”条目。数据库中也给予各抗原的功能注释。The above definitions of antigens refer to existing nomenclature (eg, "CIfA"), "sta" numbering or "NW_" numbering. Table 1 of this paper relates these three naming/numbering systems to existing SAOUHSC numbers and/or NWMN numbers. SAOUHSC numbers refer to the genome of Staphylococcus aureus strain NCTC 8325 (sequenced by Oklahoma University Health Sciences Center, GenBank published as CP000253.1; GI: 87201381), and each SAOUHSC number is listed in the " Features" section is given to the "locus_label" entry. Similarly, NWMN numbers refer to the genome of Staphylococcus aureus strain Newman (isolated from a human infection in 1952, with a stable virulence phenotype), GenBank published as AP009351.1 (GI: 150373012), each NWMN number in the genome The "features" part of the sequence is given a "locus_label" entry. Functional annotations of each antigen are also given in the database.

表1还包括本发明各抗原的GI编号。因此，不难在NCTC 8325和/或Newman菌株的公开序列数据库中找到任何这些抗原的氨基酸和核苷酸序列，但本发明不限于NCTC 8325和Newman菌株的序列。可利用金黄色葡萄球菌的几种其它菌株的基因组序列，包括MRSA菌株N315和Mu50[77]、MW2、N315、COL、MRSA252、MSSA476、RF122、USA300(极具毒力)、JH1和JH9的基因组序列。可使用标准的检索和比对技术在任何这些(或其他)基因组序列中鉴定Newman或NCTC 8325菌株的任何特定序列的同源物。此外，可利用Newman和NCTC 8325菌株的可得序列设计引物以便扩增其他菌株的同源序列。因此，本发明不限于这两种菌株，而是包括其他金黄色葡萄球菌菌株的此类变体和同源物，以及非天然变体。特定SEQ IDNO的合适变体通常包括其等位基因变体、其多态性形式、其同源物、其直向同源物、其旁系同源物、其突变体等。Table 1 also includes the GI number for each antigen of the invention. Therefore, it is not difficult to find the amino acid and nucleotide sequences of any of these antigens in the public sequence databases of NCTC 8325 and/or Newman strains, but the present invention is not limited to the sequences of NCTC 8325 and Newman strains. The genome sequences of several other strains of S. aureus are available, including the genomes of MRSA strains N315 and Mu50 [77], MW2, N315, COL, MRSA252, MSSA476, RF122, USA300 (very virulent), JH1, and JH9 sequence. Homologues to any particular sequence of the Newman or NCTC 8325 strains can be identified in any of these (or other) genomic sequences using standard searching and alignment techniques. In addition, the available sequences of Newman and NCTC 8325 strains can be used to design primers to amplify homologous sequences of other strains. Accordingly, the present invention is not limited to these two strains, but includes such variants and homologues of other S. aureus strains, as well as non-natural variants. Suitable variants of a particular SEQ IDNO generally include allelic variants thereof, polymorphic forms thereof, homologues thereof, orthologs thereof, paralogs thereof, mutants thereof, and the like.

因此，例如，与本文的SEQ ID NO相比，本发明所用多肽可包括一个或多个(如1、2、3、4、5、6、7、8、9个等)氨基酸取代，如保守取代(即用具有相关侧链的另一氨基酸取代某氨基酸)。遗传编码的氨基酸通常分为四类：(1)酸性，即，天冬氨酸、谷氨酸；(2)碱性，即，赖氨酸、精氨酸、组氨酸；(3)非极性，即，丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、甲硫氨酸、色氨酸；和(4)不带电的极性氨基酸，即，甘氨酸、天冬酰胺、谷胺酰胺、半胱氨酸、丝氨酸、苏氨酸、酪氨酸。有时将苯丙氨酸、色氨酸和酪氨酸一起称为芳族氨基酸。这些家族内各氨基酸的替换通常不会对生物活性产生重要影响。相对于SEQ ID NO序列，该多肽也可包含一个或多个(如1、2、3、4、5、6、7、8、9等)单氨基酸缺失。相对于SEQ ID NO序列，该多肽也可包含一个或多个(如1、2、3、4、5、6、7、8、9个等)插入(如1、2、3、4或5个氨基酸)。Thus, for example, polypeptides used in the invention may comprise one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.) amino acid substitutions, e.g., conservative Substitution (ie substitution of an amino acid with another amino acid having a related side chain). Genetically encoded amino acids are generally divided into four classes: (1) acidic, i.e., aspartic acid, glutamic acid; (2) basic, i.e., lysine, arginine, histidine; (3) non-acidic Polar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polar amino acids , namely, glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Together, phenylalanine, tryptophan, and tyrosine are sometimes referred to as aromatic amino acids. Substitutions of individual amino acids within these families generally do not have a significant effect on biological activity. With respect to the SEQ ID NO sequence, the polypeptide may also comprise one or more (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.) single amino acid deletions. Relative to the SEQ ID NO sequence, the polypeptide may also comprise one or more (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.) insertions (such as 1, 2, 3, 4 or 5 amino acids).

类似地，本发明所用多肽可包含某氨基酸序列，该序列：Similarly, polypeptides used in the invention may comprise an amino acid sequence that:

(a)与序列表公开的某一序列相同(即100％相同)；(a) Identical to a certain sequence disclosed in the sequence listing (i.e. 100% identical);

(b)与序列表公开的某一序列具有序列相同性(如80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；(b) having sequence identity (such as 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or higher);

(c)与(a)或(b)的序列相比，含有1、2、3、4、5、6、7、8、9或10个(或更多个)单氨基酸改变(缺失、插入、取代)，这些改变可以位于分开的位置或可以是连续的；和(c) Contains 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 (or more) single amino acid changes (deletions, insertions) compared to the sequence of (a) or (b) , substitution), these alterations may be at separate positions or may be consecutive; and

(d)用逐对比对算法与序列表中的特定序列比对时，从N-末端向C-末端的x个氨基酸的每个移动窗口(使得比对延伸到p(p＞x)个氨基酸时，存在p-x+1个此类窗口)具有至少x·y个相同的比对氨基酸，其中：x选自20、25、30、35、40、45、50、60、70、80、90、100、150、200；y选自0.50、0.60、0.70、0.75、0.80、0.85、0.90、0.91、0.92、0.93、0.94、0.95、0.96、0.97、0.98、0.99；如果x·y不是整数，则四舍五入至最接近的整数。优选的逐对比对算法是Needleman-Wunsch全局比对算法[78]，使用默认参数(如空位开放罚分＝10.0，空位延伸罚分＝0.5，使用EBLOSUM62评分矩阵)。用EMBOSS软件包中的needle工具能方便地实施这种算法[79]。(d) Each moving window of x amino acids from the N-terminus to the C-terminus (such that the alignment extends to p (p > x) amino acids when aligned with a specific sequence in the sequence listing using the pairwise alignment algorithm , there are p-x+1 such windows) with at least x.y identical aligned amino acids, wherein: x is selected from 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200; y is selected from 0.50, 0.60, 0.70, 0.75, 0.80, 0.85, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99; if x y is not an integer, are rounded to the nearest whole number. A preferred pairwise alignment algorithm is the Needleman-Wunsch global alignment algorithm [78], using default parameters (eg, gap opening penalty = 10.0, gap extension penalty = 0.5, using the EBLOSUM62 scoring matrix). This algorithm can be easily implemented with the needle tool in the EMBOSS package [79].

使用杂交多肽时，杂交体内的各抗原(即各-X-部分)可来自一种或多种菌株。例如，如果n＝2，X2可来自与X1相同的菌株，或来自不同菌株。如果n＝3，该菌株可以是(i)X1＝X2＝X3(ii)X1＝X2≠X3(iii)X1≠X2＝X3(iv)X1≠X2≠X3或(v)X1＝X3≠X2等。When hybrid polypeptides are used, each antigen (ie, each -X- moiety) within the hybrid can be from one or more strains. For example, if n=2, X2 can be from the same strain as X1 , or from a different strain. If n=3, the strain can be (i) X 1 =X 2 =X 3 (ii) X 1 =X 2 ≠X 3 (iii)X 1 ≠X 2 =X 3 (iv)X 1 ≠X 2 ≠X 3 or (v)X 1 =X 3 ≠X 2 and so on.

在(c)组内，缺失或取代可发生在N末端和/或C末端，或者可以在两末端之间。因此，截短是缺失的一个例子。截短可包括在N末端和/或C末端缺失最多40个(或更多)氨基酸。N-末端截短可除去前导肽，例如有助于在异源宿主中重组表达。C-末端截短可除去锚定序列，例如有助于在异源宿主中重组表达。Within group (c), deletions or substitutions may occur at the N-terminus and/or C-terminus, or may be in between. Thus, truncation is an example of deletion. Truncations may include deletions of up to 40 (or more) amino acids at the N-terminus and/or C-terminus. N-terminal truncation removes the leader peptide, for example to facilitate recombinant expression in a heterologous host. C-terminal truncation removes the anchor sequence, eg to facilitate recombinant expression in a heterologous host.

当抗原包含与序列表的完整金黄色葡萄球菌序列不同的序列时(例如，当它包含序列相同性＜100％的序列，或包含其片段时)，在各情况下，该抗原通常优选能引发识别完整的各金黄色葡萄球菌序列的抗体。When an antigen comprises a sequence different from the complete S. aureus sequence of the Sequence Listing (e.g. when it comprises a sequence with <100% sequence identity, or a fragment thereof), it is generally preferred in each case that the antigen elicits Antibodies that recognize the complete sequence of each S. aureus.

突变型细菌mutant bacteria

本发明还提供敲除了本发明各种抗原组的一种或多种抗原的金黄色葡萄球菌细菌。产生敲除细菌的技术是本领域熟知的，曾报道过敲除的金黄色葡萄球菌。敲除突变可位于基因的编码区，或者可位于转录控制区内(如其启动子内)。敲除突变会将编码抗原的mRNA水平降低至野生型细菌所产生水平的＜1％，优选＜0.5％，更优选＜0.1％，最优选降低至0％。The invention also provides Staphylococcus aureus bacteria knocked out of one or more antigens of the various antigen groups of the invention. Techniques for generating knockout bacteria are well known in the art, and knockout S. aureus have been reported. A knockout mutation can be located in the coding region of a gene, or it can be located within a transcriptional control region such as within its promoter. The knockout mutation will reduce the level of mRNA encoding the antigen to <1%, preferably <0.5%, more preferably <0.1%, most preferably to 0% of the level produced by wild-type bacteria.

本发明还提供其中本发明各种抗原组的一种或多种抗原具有抑制其活性的突变的金黄色葡萄球菌。编码该抗原的基因将具有改变所编码氨基酸序列的突变。突变可包括缺失、取代和/或插入，其中任何一种可涉及一个或多个氨基酸。The invention also provides S. aureus in which one or more antigens of the various antigen groups of the invention have mutations that inhibit their activity. The gene encoding the antigen will have mutations that alter the encoded amino acid sequence. Mutations may include deletions, substitutions and/or insertions, any of which may involve one or more amino acids.

本发明还提供超表达本发明抗原的细菌，例如金黄色葡萄球菌细菌。The invention also provides bacteria, such as Staphylococcus aureus bacteria, which overexpress an antigen of the invention.

本发明还提供组成型表达本发明抗原的细菌，例如金黄色葡萄球菌细菌。本发明还提供包含编码本发明抗原的基因的脑膜炎球菌，其中所述基因受诱导型启动子的控制。The invention also provides bacteria, such as Staphylococcus aureus bacteria, which constitutively express the antigens of the invention. The invention also provides a meningococcus comprising a gene encoding an antigen of the invention, wherein said gene is under the control of an inducible promoter.

免疫原性组合物和药物Immunogenic compositions and medicaments

本发明的免疫原性组合物可用作疫苗。本发明疫苗可以是预防性(即，预防感染)或治疗性(即，治疗感染)的，但一般是预防性的。The immunogenic compositions of the invention are useful as vaccines. Vaccines of the invention may be prophylactic (ie, prevent infection) or therapeutic (ie, treat infection), but are generally prophylactic.

因此，组合物可以是药学上可接受的。除抗原外，它们通常还包含其它组分，例如它们一般包含一种或多种药物载体和/或赋形剂。对这类组分的充分讨论参见参考文献273。Accordingly, the composition may be pharmaceutically acceptable. In addition to the antigen, they usually comprise other components, eg they generally comprise one or more pharmaceutical carriers and/or excipients. A full discussion of such components is found in ref. 273.

组合物通常以水性形式给予哺乳动物。然而在给药前，该组合物可以是非水性形式。例如，虽然一些疫苗制备成水性形式，然后以水性形式填充、分销和给药，但其他疫苗在制备过程中冻干，在使用时重建成水性形式。因此，本发明组合物可以是干燥制剂，例如冻干制剂。Compositions are typically administered to mammals in aqueous form. Prior to administration, however, the composition may be in non-aqueous form. For example, while some vaccines are prepared in an aqueous form, which is then filled, distributed, and administered, others are lyophilized during manufacture and reconstituted in an aqueous form at the point of use. Accordingly, compositions of the invention may be dry formulations, such as lyophilized formulations.

该组合物可含有防腐剂，如硫柳汞或2-苯氧基乙醇。然而，疫苗优选应基本不含(即，小于5μg/ml)含汞物质，如不含硫柳汞。更优选无汞的疫苗。特别优选不含防腐剂的疫苗。The composition may contain a preservative such as thimerosal or 2-phenoxyethanol. However, the vaccine should preferably be substantially free (ie, less than 5 μg/ml) of mercury-containing substances, such as free of thimerosal. Mercury-free vaccines are more preferred. Particular preference is given to vaccines which do not contain preservatives.

为了提高热稳定性，组合物可包含温度保护剂。这种制剂的进一步细节如下所述。To increase thermal stability, the composition may contain temperature protective agents. Further details of this formulation are described below.

为了控制张度，优选包含生理性盐如钠盐。优选氯化钠(NaCl)，它的浓度可以是1-20mg/ml，例如约10±2mg/ml NaCl。可以存在的其它盐，包括氯化钾、磷酸二氢钾、脱水磷酸氢二钠、氯化镁、氯化钙等。In order to control the tonicity, it is preferable to include a physiological salt such as sodium salt. Sodium chloride (NaCl) is preferred, and its concentration may be 1-20 mg/ml, for example about 10 ± 2 mg/ml NaCl. Other salts that may be present include potassium chloride, potassium dihydrogen phosphate, disodium hydrogen phosphate dehydrate, magnesium chloride, calcium chloride, and the like.

组合物的重量克分子渗透压浓度通常为200mOsm/kg-400mOsm/kg，优选240-360mOsm/kg，更优选290-310mOsm/kg。The osmolality of the composition is generally 200-400 mOsm/kg, preferably 240-360 mOsm/kg, more preferably 290-310 mOsm/kg.

组合物可含有一种或多种缓冲剂。缓冲剂一般包括：磷酸盐缓冲剂；Tris缓冲剂；硼酸盐缓冲剂；琥珀酸盐缓冲剂；组氨酸缓冲剂(特别是含氢氧化铝佐剂)；或柠檬酸缓冲剂。包含的缓冲剂浓度一般是5-20mM。Compositions may contain one or more buffering agents. Buffers generally include: phosphate buffers; Tris buffers; borate buffers; succinate buffers; histidine buffers (especially aluminum hydroxide-containing adjuvants); or citrate buffers. The buffer is typically included at a concentration of 5-20 mM.

组合物的pH通常为5.0-8.1，更常见为6.0-8.0，例如6.5-7.5，或者7.0-7.8。The pH of the composition is usually 5.0-8.1, more usually 6.0-8.0, eg 6.5-7.5, or 7.0-7.8.

该组合物优选无菌。该组合物优选无热原，如每剂量含有＜1EU(内毒素单位，标准量度)，优选每剂量＜0.1EU。该组合物优选不含谷蛋白。The composition is preferably sterile. The composition is preferably pyrogen-free, eg containing <1 EU (endotoxin unit, a standard measure) per dose, preferably <0.1 EU per dose. The composition is preferably gluten-free.

该组合物可含有一次免疫的物质，或者可含有多次免疫的物质(即‘多剂量’试剂盒)。多剂量配置优选含有防腐剂。作为多剂量组合物中包含防腐剂的替代方案(或除此之外)，该组合物可包含在装有用于取出物质的无菌接头的容器中。The composition may contain material for one immunization, or may contain material for multiple immunizations (ie a 'multi-dose' kit). Multiple dose formulations preferably contain a preservative. As an alternative (or in addition) to including a preservative in multidose compositions, the compositions may be contained in containers fitted with sterile adapters for the removal of materials.

人疫苗的给药剂量体积一般为约0.5ml，但可将一半剂量(即，约0.25ml)给予儿童。Human vaccines are typically administered in a dose volume of about 0.5 ml, although half the dose (ie, about 0.25 ml) can be given to children.

本发明的免疫原性组合物也可包含一种或多种免疫调节剂。优选地，一种或多种免疫调节剂包括一种或多种佐剂。佐剂可包括TH1佐剂和/或TH2佐剂，详述见下。The immunogenic compositions of the invention may also contain one or more immunomodulators. Preferably, the one or more immunomodulators include one or more adjuvants. Adjuvants may include TH1 adjuvants and/or TH2 adjuvants, as detailed below.

因此，本发明提供一种包含以下组合的免疫原性组合物：Accordingly, the present invention provides an immunogenic composition comprising the combination of:

(1)选自第一、第二、第三或第四抗原组(如上所述)的一种或多种抗原；和(1) one or more antigens selected from the first, second, third or fourth antigen group (as described above); and

(2)佐剂，例如氢氧化铝佐剂(例如，一种或多种抗原可吸附于氢氧化铝)。(2) Adjuvants, such as aluminum hydroxide adjuvants (eg, one or more antigens can be adsorbed to aluminum hydroxide).

例如，本发明提供包含sta006抗原和佐剂(例如，氢氧化铝佐剂)组合的免疫原性组合物。类似地，本发明提供包含sta011抗原和佐剂(例如，氢氧化铝佐剂)组合的免疫原性组合物。这些组合物最好含缓冲剂，例如组氨酸缓冲剂。For example, the invention provides immunogenic compositions comprising sta006 antigen in combination with an adjuvant (eg, aluminum hydroxide adjuvant). Similarly, the invention provides immunogenic compositions comprising the staO11 antigen in combination with an adjuvant (eg, aluminum hydroxide adjuvant). These compositions preferably contain a buffer, such as a histidine buffer.

可以用于本发明组合物的佐剂包括但不限于：Adjuvants that can be used in the compositions of the present invention include, but are not limited to:

A.含矿物质的组合物A. Mineral-containing compositions

适合用作本发明佐剂的含矿物质的组合物包括矿物盐，例如铝盐和钙盐(或其混合物)。钙盐包括磷酸钙(如参考文献80公开的“CAP”颗粒)。铝盐包括氢氧化物、磷酸盐、硫酸盐等，所述盐可采用任何合适形式(例如凝胶、结晶、非晶态形式等)。优选吸附于这些盐(例如，所有抗原可吸附)。也可将含有矿物质的组合物制成金属盐的颗粒[81]。Mineral-containing compositions suitable for use as adjuvants in the present invention include mineral salts such as aluminum and calcium salts (or mixtures thereof). Calcium salts include calcium phosphate ("CAP" particles as disclosed in reference 80). Aluminum salts include hydroxides, phosphates, sulfates, etc., which salts may take any suitable form (eg, gel, crystalline, amorphous form, etc.). Adsorption to these salts is preferred (eg, all antigens can be adsorbed). Compositions containing minerals can also be prepared as particles of metal salts [81].

可利用称为氢氧化铝和磷酸铝的佐剂。这些名称是常规名称，但仅是为方便使用，因为无一精确描述了存在的实际化学化合物(例如，参见参考文献82的第9章)。本发明可利用通常用作佐剂的任何“氢氧化物”或“磷酸盐”佐剂。称为″氢氧化铝″的佐剂一般是羟基氧化铝盐(通常至少部分为晶体)。称为″磷酸铝″的佐剂一般是羟基磷酸铝，也常常含有少量硫酸盐(即，羟基磷酸硫酸铝)。可通过沉淀获得这些佐剂，沉淀期间的反应条件和浓度影响磷酸根取代所述盐中羟基的程度。Adjuvants known as aluminum hydroxide and aluminum phosphate are available. These names are conventional, but are used for convenience only, as none accurately describe the actual chemical compound present (see, eg, Chapter 9 of ref. 82). The present invention may utilize any "hydroxide" or "phosphate" adjuvant commonly used as adjuvants. Adjuvants known as "aluminum hydroxide" are generally aluminum oxyhydroxide salts (usually at least partially crystalline). Adjuvants known as "aluminum phosphates" are generally aluminum hydroxyphosphates, often also containing small amounts of sulfate (ie, aluminum hydroxyphosphate sulfate). These adjuvants can be obtained by precipitation, during which the reaction conditions and concentrations affect the extent to which phosphate replaces the hydroxyl groups in the salt.

氢氧化铝佐剂通常是纤维形态(例如，电子透射显微照片所见的)。氢氧化铝佐剂的pI通常约11，即在生理pH下佐剂本身具有表面正电荷。据报道，pH 7.4时，氢氧化铝佐剂的吸附能力在每mg Al+++ 1.8-2.6mg蛋白质之间。Aluminum hydroxide adjuvants are usually in the form of fibers (eg, as seen in transmission electron micrographs). Aluminum hydroxide adjuvants typically have a pi of about 11, ie the adjuvant itself has a positive surface charge at physiological pH. The adsorption capacity of aluminum hydroxide adjuvants at pH 7.4 has been reported to be between 1.8–2.6 mg protein per mg Al +++ .

磷酸铝佐剂的PO4/Al摩尔比通常为0.3-1.2，优选0.8-1.2，更优选0.95±0.1。磷酸铝通常是无定形的，尤其是羟基磷酸盐。典型的佐剂是PO4/Al摩尔比为0.84-0.92的无定形羟基磷酸铝，包含0.6mg Al3+/ml。磷酸铝通常是颗粒(如在透射电子显微照片上观察到的板状形态)。抗原吸附后颗粒直径一般是0.5-20μm(如约5-10μm)。据报道，pH 7.4时磷酸铝佐剂的吸附容量为0.7-1.5毫克蛋白质/毫克Al+++。The PO 4 /Al molar ratio of the aluminum phosphate adjuvant is usually 0.3-1.2, preferably 0.8-1.2, more preferably 0.95±0.1. Aluminum phosphates are generally amorphous, especially hydroxyphosphates. A typical adjuvant is amorphous aluminum hydroxyphosphate with a PO 4 /Al molar ratio of 0.84-0.92, containing 0.6 mg Al 3+ /ml. Aluminum phosphate is usually particulate (plate-like morphology as observed on transmission electron micrographs). The particle diameter after antigen adsorption is generally 0.5-20 μm (eg, about 5-10 μm). The adsorption capacity of aluminum phosphate adjuvants at pH 7.4 has been reported to be 0.7-1.5 mg protein/mg Al +++ .

磷酸铝的零点电荷(PZC)与磷酸根对羟基的取代程度逆相关，这种取代程度可能取决于通过沉淀制备盐所用的反应条件和反应物浓度。也通过改变溶液中游离磷酸根离子的浓度(更多磷酸根＝更多酸性PZC)或加入缓冲剂如组氨酸缓冲剂(使PZC碱性更强)改变PZC。本发明所用的磷酸铝的PZC通常为4.0-7.0，更优选5.0-6.5，例如约5.7。The point zero charge (PZC) of aluminum phosphate is inversely related to the degree of substitution of phosphate for hydroxyl groups, which may depend on the reaction conditions and reactant concentrations used to prepare the salt by precipitation. PZC is also altered by changing the concentration of free phosphate ions in solution (more phosphate = more acidic PZC) or adding a buffer such as histidine buffer (making PZC more basic). The aluminum phosphate used in the present invention typically has a PZC of 4.0-7.0, more preferably 5.0-6.5, eg about 5.7.

如下所示，优选将金黄色葡萄球菌抗原(除了IsdA、Sta019和Sta073)吸附于氢氧化铝佐剂，尤其是在多蛋白质组合中(其中所有抗原可吸附)。此类含佐剂组合物中包含组氨酸缓冲剂是有用的。As shown below, adsorption of S. aureus antigens (except IsdA, Sta019 and Sta073) to aluminum hydroxide adjuvant is preferred, especially in multi-protein combinations (where all antigens are adsorbable). It is useful to include a histidine buffer in such adjuvanted compositions.

用于制备本发明组合物的铝盐悬浮液可以，但不一定含有缓冲剂(如磷酸盐或组氨酸或Tris缓冲液)。该悬浮液优选无菌且无热原。悬浮液可含有游离的水合磷酸根离子，如存在浓度为1.0-20mM，优选5-15mM，更优选约10mM。该悬浮液也可含有氯化钠。The aluminum salt suspension used to prepare the compositions of the invention may, but need not, contain a buffer (such as phosphate or histidine or Tris buffer). The suspension is preferably sterile and pyrogen-free. The suspension may contain free hydrated phosphate ions, eg, present at a concentration of 1.0-20 mM, preferably 5-15 mM, more preferably about 10 mM. The suspension may also contain sodium chloride.

本发明可使用氢氧化铝和磷酸铝的混合物。在这种情况下，磷酸铝比氢氧化铝多，例如重量比为至少2∶1，例如≥5∶1、≥6∶1、≥7∶1、≥8∶1、≥9∶1等。Mixtures of aluminum hydroxide and aluminum phosphate can be used in the present invention. In this case there is more aluminum phosphate than aluminum hydroxide, eg in a weight ratio of at least 2:1, eg >5:1, >6:1, >7:1, >8:1, >9:1 etc.

给予患者的组合物中Al+++的浓度优选小于10mg/ml，例如≤5mg/ml、≤4mg/ml、≤3mg/ml、≤2mg/ml、≤1mg/ml等。优选范围是0.3-1mg/ml。最大值优选0.85mg/剂。The concentration of Al +++ in the composition administered to the patient is preferably less than 10 mg/ml, such as ≤5 mg/ml, ≤4 mg/ml, ≤3 mg/ml, ≤2 mg/ml, ≤1 mg/ml, etc. A preferred range is 0.3-1 mg/ml. The maximum value is preferably 0.85 mg/dose.

B.油乳液B. Oil emulsion

适合用作本发明佐剂的油乳液组合物包含角鲨烯-水乳剂，如MF59[参考文献82第10章；也见参考文献83](5％角鲨烯、0.5％吐温80和0.5％司盘85，用微流化床配制成亚微米颗粒)。也可以使用完全弗氏佐剂(CFA)和不完全弗氏佐剂(IFA)。Oil emulsion compositions suitable for use as adjuvants in the present invention comprise squalene-water emulsions such as MF59 [Chapter 10 of ref. 82; see also ref. 83] (5% squalene, 0.5% Tween 80 and 0.5 % Span 85, formulated into submicron particles using a microfluidizer). Complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA) can also be used.

已知各种水包油乳液，它们通常包含至少一种油和至少一种表面活性剂，所述油和表面活性剂是可生物降解(可代谢)和生物相容的。乳液中油滴的直径通常小于5μm，最好具有亚微米直径，通过微流化床实现这种小尺寸以提供稳定乳液。优选尺寸小于220nm的液滴，因为其可进行过滤灭菌。Various oil-in-water emulsions are known, which generally comprise at least one oil and at least one surfactant which are biodegradable (metabolizable) and biocompatible. The diameter of the oil droplets in the emulsion is usually less than 5 μm, preferably with a submicron diameter, and this small size is achieved by a microfluidized bed to provide a stable emulsion. Droplets with a size of less than 220 nm are preferred because they can be filter sterilized.

所述乳液可以包含如动物(如鱼)或植物来源的油。植物油的来源包括坚果、种籽和谷物。最常用的花生油、大豆油、椰油和橄榄油是坚果油的代表例子。可以使用例如获自霍霍巴豆的霍霍巴油。种籽油包括红花油、棉籽油、葵花籽油、芝麻籽油等。在谷物油中，最常用的是玉米油，但也可以使用其它谷类的油，如小麦、燕麦、黑麦、稻、画眉草(teff)、黑小麦(triticale)等。可从坚果和种籽油开始，通过水解、分离和酯化合适物质制备甘油和1，2-丙二醇的6-10碳脂肪酸酯(不是种籽油中天然产生的)。来自哺乳动物乳汁的脂肪和油类是可代谢的，因此可以用于实施本发明。由动物来源获得纯油必需的分离、纯化、皂化和其它方法的过程是本领域熟知的。大多数鱼类含有容易回收的可代谢油。例如，鳕鱼肝油、鲨鱼肝油和如鲸蜡的鲸油是可以用于本发明的几种鱼油的例子。通过生化途径用5-碳异戊二烯单位合成许多支链油，它们总称为萜类。鲨鱼肝油含有称为角鲨烯的支链不饱和萜类化合物，2，6，10，15，19，23-六甲基-2，6，10，14，18，22-二十四碳六烯，本文特别优选该萜类化合物。角鲨烯的饱和类似物角鲨烷也是优选的油。鱼油，包括鲨烯和鲨烷，易于从商业来源获得，或可以通过本领域已知的方法获得。其它优选油是生育酚(见下)。可以使用油的混合物。The emulsion may comprise, for example, oils of animal (eg fish) or vegetable origin. Sources of vegetable oils include nuts, seeds and grains. The most commonly used peanut oil, soybean oil, coconut oil and olive oil are representative examples of nut oils. Jojoba oil obtained, for example, from jojoba beans can be used. Seed oils include safflower oil, cottonseed oil, sunflower oil, sesame seed oil, and others. Of the grain oils, corn oil is most commonly used, but oils from other cereals such as wheat, oats, rye, rice, teff, triticale, etc. may also be used. 6-10 carbon fatty acid esters of glycerol and 1,2-propanediol (not naturally occurring in seed oils) can be prepared starting from nut and seed oils by hydrolysis, isolation and esterification of the appropriate species. Fats and oils from mammalian milk are metabolizable and thus can be used in the practice of the present invention. The processes of isolation, purification, saponification and other methods necessary to obtain pure oils from animal sources are well known in the art. Most fish contain metabolizable oils that are easily recovered. For example, cod liver oil, shark liver oil, and whale oils such as spermaceti are examples of several fish oils that may be used in the present invention. A number of branched-chain oils are synthesized by biochemical pathways using 5-carbon isoprene units, which are collectively referred to as terpenes. Shark liver oil contains branched unsaturated terpenoids called squalene, 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexa Alkenes, the terpenoids are particularly preferred herein. Squalane, the saturated analog of squalene, is also a preferred oil. Fish oils, including squalene and squalane, are readily available from commercial sources or can be obtained by methods known in the art. Other preferred oils are tocopherols (see below). Mixtures of oils can be used.

可通过其“HLB”(亲水/亲脂平衡)对表面活性剂分类。本发明的优选表面活性剂的HLB为至少10，优选至少15，更优选至少16。可以用于本发明的表面活性剂包括但不限于：聚氧乙烯脱水山梨糖醇酯表面活性剂(通常称为吐温)，特别是聚山梨酯20和聚山梨酯80；以商品名DOWFAXTM出售的环氧乙烷(EO)、环氧丙烷(PO)和/或环氧丁烷(BO)的共聚物，如直链EP/PO嵌段共聚物；重复的乙氧基(氧-1，2-乙二基)数量不同的辛苯聚醇，特别感兴趣的是辛苯聚醇9(曲通(Triton)X-100，或叔辛基苯氧基聚乙氧基乙醇)；(辛基苯氧基)聚乙氧基乙醇(IGEPAL CA-630/NP-40)；磷脂，如磷脂酰胆碱(卵磷脂)；壬酚乙醇酯，如TergitolTM NP系列；衍生自月桂醇、鲸蜡醇、硬脂醇和油醇的聚氧乙烯脂肪醚(称为苄泽(Brij)表面活性剂)，如三甘醇单月桂基醚(苄泽30)；以及脱水山梨糖醇酯(通常称为司盘(SPAN))，如脱水山梨糖醇三油酸酯(司盘85)和脱水山梨糖醇单月桂酸酯。优选非离子型表面活性剂。乳液中包含的优选表面活性剂是吐温80(聚氧乙烯去水山梨糖醇单油酸酯)、司盘85(去水山梨糖醇三油酸酯)、卵磷脂和曲通X-100。Surfactants can be classified by their "HLB" (hydrophilic/lipophilic balance). Preferred surfactants of the invention have an HLB of at least 10, preferably at least 15, more preferably at least 16. Surfactants that may be used in the present invention include, but are not limited to: polyoxyethylene sorbitan ester surfactants (commonly known as Tweens), especially polysorbate 20 and polysorbate 80; sold under the tradename DOWFAX ™ Sold copolymers of ethylene oxide (EO), propylene oxide (PO) and/or butylene oxide (BO), such as linear EP/PO block copolymers; repeating ethoxyl (oxygen-1 , 2-ethylenediyl) varying amounts of octoxynol, of particular interest is octoxynol 9 (Triton X-100, or tert-octylphenoxypolyethoxyethanol); ( octylphenoxy) polyethoxyethanol (IGEPAL CA-630/NP-40); phospholipids, such as phosphatidylcholine (lecithin); nonanolates, such as Tergitol TM NP series; derived from lauryl alcohol, Polyoxyethylene fatty ethers of cetyl, stearyl, and oleyl alcohols (known as Brij surfactants), such as triethylene glycol monolauryl ether (Brij 30); and sorbitan esters (often Known as Span (SPAN)), such as sorbitan trioleate (Span 85) and sorbitan monolaurate. Nonionic surfactants are preferred. Preferred surfactants included in the emulsion are Tween 80 (polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate), lecithin and Triton X-100 .

可使用表面活性剂的混合物，如吐温80/司盘85混合物。聚氧乙烯去水山梨糖醇酯，如聚氧乙烯去水山梨糖醇单油酸酯(吐温80)和辛苯聚醇如叔辛基苯氧基聚乙氧基乙醇(曲通X-100)的组合也适合。另一种有用的组合包含月桂醇聚醚-9和聚氧乙烯去水山梨糖醇酯和/或辛苯聚醇。Mixtures of surfactants can be used, such as a Tween 80/Span 85 mixture. Polyoxyethylene sorbitan esters such as polyoxyethylene sorbitan monooleate (Tween 80) and octoxynols such as t-octylphenoxypolyethoxyethanol (Triton X- 100) combinations are also suitable. Another useful combination comprises laureth-9 and polyoxyethylene sorbitan ester and/or octoxynol.

优选的表面活性剂用量(重量％)为：聚氧乙烯去水山梨糖醇酯(如吐温80)0.01-1％，特别是约0.1％；辛基-或壬基苯氧基聚氧乙醇(如曲通X-100或曲通系列的其它洗涤剂)0.001-0.1％，特别是0.005-0.02％；聚氧乙烯醚(如月桂醇聚醚9)0.1-20％，优选0.1-10％，特别是0.1-1％或约0.5％。The preferred surfactant dosage (% by weight) is: polyoxyethylene sorbitan ester (such as Tween 80) 0.01-1%, especially about 0.1%; octyl- or nonylphenoxypolyoxyethanol (such as Triton X-100 or other detergents of Triton series) 0.001-0.1%, especially 0.005-0.02%; polyoxyethylene ether (such as laureth 9) 0.1-20%, preferably 0.1-10% , especially 0.1-1% or about 0.5%.

优选乳液佐剂的平均液滴大小为＜1μm，例如≤750nm、≤500nm、≤400nm、≤300nm、≤250nm、≤220nm、≤200nm或更小。可通过诸如微流化等技术方便地获得这些液滴尺寸。Preferably the average droplet size of the emulsion adjuvant is <1 μm, eg ≤750 nm, ≤500 nm, ≤400 nm, ≤300 nm, ≤250 nm, ≤220 nm, ≤200 nm or smaller. These droplet sizes are conveniently obtained by techniques such as microfluidization.

本发明所用的具体水包油乳液佐剂包括但不限于：Specific oil-in-water emulsion adjuvants used in the present invention include, but are not limited to:

●角鲨烯、吐温80和司盘85的亚微米乳液。所述乳液的体积组成可以是约5％角鲨烯、约0.5％聚山梨酯80和约0.5％司盘85。以重量计，这些比例为4.3％角鲨烯、0.5％聚山梨酯80和0.48％司盘85。该佐剂称为‘MF59’[84-86]，参考文献87的第10章和参考文献88的第12章更详细地描述了该佐剂。MF59乳液宜包含柠檬酸根离子，例如10mM柠檬酸钠缓冲液。● Submicron emulsion of squalene, Tween 80 and Span 85. The emulsion may have a composition by volume of about 5% squalene, about 0.5% polysorbate 80, and about 0.5% Span 85. These proportions are 4.3% squalene, 0.5% polysorbate 80 and 0.48% Span 85 by weight. This adjuvant, called 'MF59' [84-86], is described in more detail in Chapter 10 of ref. 87 and in Chapter 12 of ref. 88. The MF59 emulsion preferably contains citrate ions, eg 10 mM sodium citrate buffer.

●鲨烯、生育酚和聚山梨酯80(吐温80)的乳液。所述乳液可包含磷酸盐缓冲盐水。它也可含有司盘85(如1％)和/或卵磷脂。这些乳液可含有2-10％鲨烯、2-10％生育酚和0.3-3％吐温80，鲨烯∶生育酚的重量比优选≤1，因为这能提供更稳定的乳液。角鲨烯和吐温80的体积比可以约为5∶2，或者重量比约为11∶5。可通过下述方法制备一种这样的乳液：将吐温80溶解于PBS得到2％溶液，然后将90ml该溶液与5g DL-α-生育酚和5ml鲨烯的混合物混合，然后使该混合物微流体化。得到的乳液可含有(如)平均直径为100-250nm，优选约180nm的亚微米油滴。该乳液也可含有3-脱-O-酰化单磷酰脂质A(‘3d-MPL’)。此类的另一种有用乳液可包含(每个人用剂量)0.5-10mg鲨烯、0.5-11mg生育酚和0.1-4mg聚山梨酯80[89]。- Emulsion of squalene, tocopherol and polysorbate 80 (Tween 80). The emulsion may comprise phosphate buffered saline. It may also contain Span 85 (eg 1%) and/or lecithin. These emulsions may contain 2-10% squalene, 2-10% tocopherol and 0.3-3% Tween 80, the squalene:tocopherol weight ratio is preferably ≤1 as this provides a more stable emulsion. The volume ratio of squalene and Tween 80 may be about 5:2, or about 11:5 by weight. One such emulsion can be prepared by dissolving Tween 80 in PBS to obtain a 2% solution, then mixing 90 ml of this solution with a mixture of 5 g DL-α-tocopherol and 5 ml squalene, and then allowing the mixture to slightly Fluid. The resulting emulsion may contain, for example, submicron oil droplets having an average diameter of 100-250 nm, preferably about 180 nm. The emulsion may also contain 3-de-O-acylated monophosphoryl lipid A ('3d-MPL'). Another useful emulsion of this type may contain (per human dose) 0.5-10 mg squalene, 0.5-11 mg tocopherol, and 0.1-4 mg polysorbate 80 [89].

●鲨烯、生育酚和曲通洗涤剂(如曲通X-100)的乳液。该乳液也可包含3d-MPL(见下)。所述乳液可包含磷酸盐缓冲液。• Emulsions of squalene, tocopherol and Triton detergent (eg Triton X-100). The emulsion may also contain 3d-MPL (see below). The emulsion may comprise phosphate buffered saline.

●含有聚山梨酯(如聚山梨酯80)、曲通洗涤剂(如曲通X-100)和生育酚(如琥珀酸α-生育酚)的乳液。该乳液可包含这三种组分，其质量比约为75∶11∶10(如750μg/ml聚山梨酯80、110μg/ml曲通X-100和100μg/ml琥珀酸α-生育酚)，这些浓度应包括抗原中这些组分的贡献。所述乳液还可包含角鲨烯。该乳液也可包含3d-MPL(见下)。所述水相可包含磷酸盐缓冲液。• Emulsions containing polysorbate (eg polysorbate 80), Triton detergent (eg Triton X-100) and tocopherol (eg alpha-tocopheryl succinate). The emulsion may comprise these three components in a mass ratio of about 75:11:10 (such as 750 μg/ml polysorbate 80, 110 μg/ml Triton X-100 and 100 μg/ml succinic acid α-tocopherol), These concentrations should include the contribution of these components in the antigen. The emulsion may also contain squalene. The emulsion may also contain 3d-MPL (see below). The aqueous phase may comprise a phosphate buffer.

●鲨烷、聚山梨酯80和泊洛沙姆401(″普流罗尼克TM L121″)的乳液。可以用pH 7.4的磷酸盐缓冲盐水配制所述乳液。该乳液是有用的胞壁酰二肽递送载体，已与用″SAF-I″佐剂(0.05-1％Thr-MDP、5％鲨烯、2.5％普流罗尼克L121和0.2％聚山梨酸酯80)配的苏氨酰基-MDP[90]一起使用。也可不与Thr-MDP一起使用，例如用″AF″佐剂(5％鲨烯、1.25％普流罗尼克L121和0.2％聚山梨酸酯80)[91]。优选微流体化。• Emulsion of squalane, polysorbate 80 and poloxamer 401 ("Pluronic ™ L121"). The emulsion can be formulated in phosphate buffered saline at pH 7.4. The emulsion is a useful delivery vehicle for muramyl dipeptide, which has been combined with "SAF-I" adjuvant (0.05-1% Thr-MDP, 5% squalene, 2.5% pluronic L121 and 0.2% polysorbate Ester 80) with threonyl-MDP [90] used together. It can also be used without Thr-MDP, eg with "AF" adjuvant (5% squalene, 1.25% pluronic L121 and 0.2% polysorbate 80) [91]. Microfluidization is preferred.

●含有鲨烯、水性溶剂、聚氧乙烯烷基醚亲水性非离子型表面活性剂(如聚氧乙烯(12)十六十八醚)和疏水性非离子型表面活性剂(如去水山梨糖醇酯或二缩甘露醇酯，如去水山梨糖醇单油酸酯或‘司盘80’)的乳液。该乳液优选为热可逆的和/或其中至少90％油滴(以体积计)小于200nm[92]。该乳液也可含有以下一种或多种物质：糖醇；低温保护剂(例如，糖，如十二烷基麦芽苷和/或蔗糖)；和/或烷基聚糖苷(alkylpolyglycoside)。该乳液可包含TLR4激动剂[93]。这类乳液可冻干。●Contains squalene, aqueous solvent, polyoxyethylene alkyl ether hydrophilic nonionic surfactant (such as polyoxyethylene (12) cetostearyl ether) and hydrophobic nonionic surfactant (such as dehydrating Emulsions of sorbitan esters or mannide esters, such as sorbitan monooleate or 'Span 80'). The emulsion is preferably thermoreversible and/or wherein at least 90% of the oil droplets (by volume) are smaller than 200 nm [92]. The emulsion may also contain one or more of the following: sugar alcohols; cryoprotectants (eg, sugars such as lauryl maltoside and/or sucrose); and/or alkylpolyglycosides. The emulsion may contain a TLR4 agonist [93]. Such emulsions can be lyophilized.

●角鲨烯、泊洛沙姆105和Abil-Care的乳液[94]。含佐剂疫苗中这些组分的终浓度(重量)是5％鲨烯、4％泊洛沙姆105(普流罗尼多元醇)和2％Abil-Care 85(双-PEG/PPG-16/16 PEG/PPG-16/16二甲硅油；辛酸/癸酸甘油三酯)。• Emulsions of squalene, poloxamer 105, and Abil-Care [94]. The final concentrations (by weight) of these components in the adjuvanted vaccine were 5% squalene, 4% Poloxamer 105 (Pluronic polyol) and 2% Abil-Care 85 (bis-PEG/PPG-16 /16 PEG/PPG-16/16 Simethicone; Caprylic/Capric Triglyceride).

●含有0.5-50％油、0.1-10％磷脂和0.05-5％非离子型表面活性剂的乳液。如参考文献95所述，优选的磷脂组分是磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰肌醇、磷脂酰甘油、磷脂酸、鞘磷脂和心磷脂。优选亚微米液滴尺寸。• Emulsions containing 0.5-50% oil, 0.1-10% phospholipids and 0.05-5% non-ionic surfactants. As described in reference 95, preferred phospholipid components are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin and cardiolipin. Submicron droplet sizes are preferred.

●不可代谢油(如轻质矿物油)和至少一种表面活性剂(如卵磷脂、吐温80或司盘80)的亚微米水包油乳液。可包含添加剂，例如QuilA皂苷、胆固醇、皂苷-亲脂体偶联物(如通过葡糖醛酸的羧基将脂族胺加到脱酰基皂苷上而产生的GPI-0100，参见参考文献96、二甲基二-十八烷基溴化铵和/或N，N-二-十八烷基-N，N-双(2-羟乙基)丙二胺。• A submicron oil-in-water emulsion of a non-metabolizable oil (such as light mineral oil) and at least one surfactant (such as lecithin, Tween 80 or Span 80). Additives may be included such as QuilA saponins, cholesterol, saponin-lipophile conjugates (such as GPI-0100 produced by adding an aliphatic amine to a deacylated saponin via the carboxyl group of glucuronic acid, see ref. 96, 2 Methyldioctadecylammonium bromide and/or N,N-dioctadecyl-N,N-bis(2-hydroxyethyl)propylenediamine.

●皂苷(如QuilA或QS21)和固醇(如胆固醇)结合成螺旋胶束的乳液[97]。● Emulsions of saponins (such as QuilA or QS21) and sterols (such as cholesterol) bound into helical micelles [97].

●包含矿物油、非离子亲脂性乙氧基化脂肪醇和非离子亲水性表面活性剂(例如，乙氧基化脂肪醇和/或聚氧乙烯-聚氧丙烯嵌段共聚物)的乳液[98]。●Emulsions containing mineral oil, nonionic lipophilic ethoxylated fatty alcohols, and nonionic hydrophilic surfactants (eg, ethoxylated fatty alcohols and/or polyoxyethylene-polyoxypropylene block copolymers) [98 ].

●包含矿物油、非离子亲脂水性乙氧基化脂肪醇和非离子亲脂性表面活性剂(例如，乙氧基化脂肪醇和/或聚氧乙烯-聚氧丙烯嵌段共聚物)的乳液[98]。Emulsions containing mineral oil, nonionic lipophilic aqueous ethoxylated fatty alcohols, and nonionic lipophilic surfactants (eg, ethoxylated fatty alcohols and/or polyoxyethylene-polyoxypropylene block copolymers) [98 ].

在一些实施方式中，可在递送时临时混合乳液与抗原，因此所述佐剂和抗原可单独地保存在包装或分销的疫苗中，以便在使用时配制成最终制剂。在其它实施方式中，在生产过程中混合乳液与抗原，因此所述组合物以液体佐剂形式包装。所述抗原通常是水性形式，以便最终通过混合两种液体制备疫苗。所述两种液体的混合体积比可变(例如5∶1-1∶5)，但通常约为1∶1。如果上述对具体乳液的说明给出了组分浓度，这些浓度通常用于非稀释组合物，因此与抗原溶液混合后浓度降低。In some embodiments, the emulsion and antigen can be mixed extemporaneously at the time of delivery, so that the adjuvant and antigen can be kept separately in the packaged or distributed vaccine to be formulated into the final formulation at the time of use. In other embodiments, the emulsion is mixed with the antigen during manufacture, so the composition is packaged in a liquid adjuvant. The antigen is usually in aqueous form so that the vaccine is finally prepared by mixing the two liquids. The mixed volume ratio of the two liquids can vary (eg, 5:1-1:5), but is usually about 1:1. Where component concentrations are given in the above description for a particular emulsion, these concentrations are generally for non-diluted compositions and thus reduced in concentration upon admixture with the antigen solution.

如果组合物包含生育酚，可采用α、β、γ、δ、ε或ξ生育酚中的任何一种，但优选α-生育酚。生育酚可取多种形式，例如不同的盐和/或异构体。盐包括有机盐，例如琥珀酸盐、乙酸盐、烟酸盐等。可同时采用D-α-生育酚和DL-α-生育酚。用于老年患者(如年龄大于60岁或更大的患者)的疫苗中宜包含生育酚，因为据报道维生素E在此患者群体中对免疫应答有正面作用[99]。它们也具有抗氧化特性，这种特性有助于稳定该乳液[100]。优选的α-生育酚是DL-α-生育酚，此种生育酚的优选盐是琥珀酸盐。发现琥珀酸盐在体内能与TNF相关配体协作。If the composition comprises tocopherol, any of alpha, beta, gamma, delta, epsilon or zeta tocopherol may be used, but alpha-tocopherol is preferred. Tocopherol can take various forms, such as different salts and/or isomers. Salts include organic salts such as succinate, acetate, nicotinate, and the like. Both D-α-tocopherol and DL-α-tocopherol can be used simultaneously. Inclusion of tocopherol in vaccines used in elderly patients (eg, those aged 60 years or older) is desirable because vitamin E has been reported to have a positive effect on the immune response in this patient population [99]. They also have antioxidant properties that help stabilize the emulsion [100]. The preferred alpha-tocopherol is DL-alpha-tocopherol and the preferred salt of this tocopherol is succinate. Succinate was found to cooperate with TNF-related ligands in vivo.

C.皂苷制剂[参考文献82的第22章]C. Saponin Preparations [Chapter 22 of Ref. 82]

皂苷制剂也可以用作本发明的佐剂。皂苷是在许多种类植物的树皮、叶、茎干、根甚至花中发现的甾醇糖苷和三萜糖苷的异质群体。已广泛研究了作为佐剂的皂树(Quillaia saponaria Molina)树皮的皂苷。皂苷也可购自丽花菝葜(Smilax ornata)(墨西哥菝葜)、满天星(Gypsophilla paniculata)(婚纱花)和肥皂草(Saponaria officianalis)(皂根)。皂苷佐剂制剂包括纯化制剂如QS21，以及脂质制剂如ISCOM。QS21以商标StimulonTM出售。Saponin preparations can also be used as adjuvants in the present invention. Saponins are a heterogeneous group of steryl and triterpene glycosides found in the bark, leaves, stems, roots and even flowers of many species of plants. Saponins from the bark of Quillaia saponaria Molina have been extensively studied as adjuvants. Saponins are also commercially available from Smilax ornata (sarsaparilla), Gypsophilla paniculata (wedding flower), and Saponaria officianalis (soap root). Saponin adjuvant formulations include purified formulations such as QS21, and lipid formulations such as ISCOM. QS21 is sold under the trademark Stimulon ™ .

已采用HPLC和RP-HPLC纯化皂苷组合物。已鉴定了用这些技术纯化的特定组分，包括QS7、QS17、QS18、QS21、QH-A、QH-B和QH-C。所述皂苷优选QS21。制备QS21的方法参见参考文献101。皂苷制剂也可以包含甾醇，如胆固醇[102]。Saponin compositions have been purified using HPLC and RP-HPLC. Specific fractions purified by these techniques have been identified, including QS7, QS17, QS18, QS21, QH-A, QH-B, and QH-C. The saponin is preferably QS21. The method for preparing QS21 can be found in reference 101. Saponin preparations may also contain sterols, such as cholesterol [102].

皂苷和胆固醇的组合可用于形成称为免疫刺激复合物(ISCOM)的独特颗粒[参考文献82的第23章]。ISCOM通常还包含磷脂，如磷脂酰乙醇胺或磷脂酰胆碱。任何已知的皂苷均可以用于ISCOM中。ISCOM优选包含QuilA、QHA和QHC中的一种或多种。参考文献102-104中进一步描述了ISCOM。任选地，ISCOM可以不含其它洗涤剂[105]。Combinations of saponins and cholesterol can be used to form unique particles called immunostimulatory complexes (ISCOMs) [Chapter 23 of ref. 82]. ISCOMs usually also contain phospholipids, such as phosphatidylethanolamine or phosphatidylcholine. Any known saponin can be used in ISCOM. The ISCOM preferably comprises one or more of QuilA, QHA and QHC. ISCOM is further described in references 102-104. Optionally, ISCOM can be free of other detergents [105].

开发基于皂苷的佐剂的综述可参见参考文献106和107。Reviews of the development of saponin-based adjuvants can be found in refs 106 and 107.

D.病毒体和病毒样颗粒D. Virions and virus-like particles

病毒体和病毒样颗粒(VLP)也可以用作本发明的佐剂。这些结构通常包含任选与磷脂组合或一起配制的一种或多种病毒蛋白质。其通常无病原性，不能复制，且通常不含任何天然病毒基因组。所述病毒蛋白可重组生成或分离自全病毒。这些适用于病毒体或VLP的病毒蛋白包括来自流感病毒(例如HA或NA)、乙肝病毒(例如核心蛋白或衣壳蛋白)、戊肝病毒、麻疹病毒、辛德比斯病毒、轮状病毒、口蹄疫病毒、逆转录病毒、诺沃克病毒、人乳头状瘤病毒、HIV、RNA-噬菌体、Qβ-噬菌体(如外壳蛋白)、GA-噬菌体、fr-噬菌体、AP205噬菌体和Ty(如反转录转座子Ty蛋白p1)的蛋白。VLP在参考文献108-113中有进一步描述。病毒体在(例如)参考文献114中有进一步描述。Virosomes and virus-like particles (VLPs) can also be used as adjuvants in the present invention. These structures generally comprise one or more viral proteins optionally combined or formulated with phospholipids. It is usually non-pathogenic, cannot replicate, and usually does not contain any native viral genome. The viral proteins can be recombinantly produced or isolated from whole viruses. These viral proteins suitable for use in virions or VLPs include those from influenza virus (e.g. HA or NA), hepatitis B virus (e.g. core protein or capsid protein), hepatitis E virus, measles virus, Sindbis virus, rotavirus, foot-and-mouth disease Viruses, retroviruses, Norwalk virus, HPV, HIV, RNA-phages, Qβ-phages (e.g. coat protein), GA-phages, fr-phages, AP205 phages and Ty (e.g. retrotransposition The protein of sub-Ty protein p1). VLPs are further described in refs 108-113. Virosomes are further described, for example, in reference 114.

E.细菌或微生物衍生物E. Bacterial or microbial derivatives

适用于本发明的佐剂包括细菌或微生物衍生物，如肠细菌的脂多糖(LPS)的无毒衍生物、脂质A衍生物、免疫刺激性寡核苷酸和ADP-核糖基化毒素及其脱毒衍生物。Adjuvants suitable for use in the present invention include bacterial or microbial derivatives, such as non-toxic derivatives of lipopolysaccharide (LPS) of enterobacteria, lipid A derivatives, immunostimulatory oligonucleotides and ADP-ribosylating toxins and its detoxified derivatives.

LPS的无毒衍生物包括单磷酰脂质A(MPL)和3-O-脱酰基MPL(3dMPL)。3dMPL是3脱-O-酰化单磷酰脂质A与4、5或6酰化链的混合物。3脱-O-酰化单磷酰脂质A的优选“小颗粒”形式见参考文献115所述。3dMPL的这种“小颗粒”小到足以在过滤除菌时通过0.22μm膜[115]。其它无毒LPS衍生物包括单磷酰脂质A模拟物，如氨基烷基氨基葡萄糖苷磷酸酯衍生物，例如RC-529[116，117]。Nontoxic derivatives of LPS include monophosphoryl lipid A (MPL) and 3-O-deacylated MPL (3dMPL). 3dMPL is a mixture of 3 de-O-acylated monophosphoryl lipid A with 4, 5 or 6 acylated chains. 3 Preferred "small particle" forms of de-O-acylated monophosphoryl lipid A are described in reference 115. This "small particle" of 3dMPL is small enough to pass through a 0.22 μm membrane upon filter sterilization [115]. Other non-toxic LPS derivatives include monophosphoryl lipid A mimetics such as aminoalkyl glucosamine phosphate derivatives eg RC-529 [116,117].

脂质A衍生物包括大肠杆菌(Escherichia coli)，如OM-174的脂质A衍生物。(例如)参考文献118和119中描述了OM-174。Lipid A derivatives include lipid A derivatives of Escherichia coli, such as OM-174. OM-174 is described, for example, in references 118 and 119.

适合用作本发明佐剂的免疫刺激性寡核苷酸包括含CpG基序的核苷酸序列(含有通过磷酸键与鸟苷连接的非甲基化胞嘧啶的二核苷酸序列)。含回文或聚(dG)序列的双链RNA和寡核苷酸也显示具有免疫刺激作用。Immunostimulatory oligonucleotides suitable for use as adjuvants in the present invention include CpG motif-containing nucleotide sequences (dinucleotide sequences containing an unmethylated cytosine linked to a guanosine by a phosphate bond). Double-stranded RNA and oligonucleotides containing palindromic or poly(dG) sequences have also been shown to be immunostimulatory.

CpG可以包含核苷酸修饰/类似物，如硫代磷酸酯修饰，可以是双链或单链。参考文献120、121和122公开了可能的类似物取代，例如用2’-脱氧-7-脱氮鸟苷取代鸟苷。参考文献123-128中进一步讨论了CpG寡核苷酸的佐剂作用。CpGs can contain nucleotide modifications/analogues, such as phosphorothioate modifications, and can be double-stranded or single-stranded. References 120, 121 and 122 disclose possible analogue substitutions such as 2'-deoxy-7-deazaguanosine for guanosine. The adjuvant role of CpG oligonucleotides is further discussed in refs. 123-128.

所述CpG序列可以导向TLR9，例如基序GTCGTT或TTCGTT[129]。CpG序列可特异性诱导Th1免疫应答，如CpG-A ODN，或更特异地诱导B细胞应答，如CpG-B ODN。参考文献130-132中讨论了CpG-A和CpG-BODN。CpG优选为CpG-A ODN。The CpG sequence can be directed to TLR9, eg the motif GTCGTT or TTCGTT [129]. CpG sequences can specifically induce Th1 immune responses, such as CpG-A ODN, or more specifically induce B cell responses, such as CpG-B ODN. CpG-A and CpG-BODN are discussed in references 130-132. The CpG is preferably a CpG-A ODN.

CpG寡核苷酸优选构建成5’末端可被受体识别。任选将两个CpG寡核苷酸序列的3’端相连接形成免疫聚体。参见例如，参考文献129和133-135。CpG oligonucleotides are preferably constructed so that the 5' end is recognized by the receptor. Optionally, the 3' ends of the two CpG oligonucleotide sequences are linked to form an immunomer. See, eg, refs. 129 and 133-135.

有用的CpG佐剂是CpG7909，也称为ProMuneTM(科雷制药集团公司(Coley Pharmaceutical Group，Inc.))。另一种是CpG1826。或者或此外，为使用CpG序列，可使用TpG序列[136]，这些寡核苷酸可不含非甲基化CpG基序。免疫刺激性寡核苷酸可能富含嘧啶。例如，其可包含多个连续胸苷核苷酸(例如，TTTT，见参考文献136)，和/或其可具有含＞25％胸苷(例如，＞35％、＞40％、＞50％、＞60％、＞80％，等)的核苷酸组成。例如，其可包含多个连续胞嘧啶核苷酸(例如，CCCC，见参考文献136)，和/或其可具有含＞25％胞嘧啶(例如，＞35％、＞40％、＞50％、＞60％、＞80％，等)胸苷的核苷酸组成。这些寡核苷酸可不含未甲基化的CpG基序。免疫刺激性寡核苷酸通常包含至少20个核苷酸。其可包含少于100个核苷酸。A useful CpG adjuvant is CpG7909, also known as ProMune ™ (Coley Pharmaceutical Group, Inc.). The other is CpG1826. Alternatively or additionally, to use CpG sequences, TpG sequences may be used [136] and these oligonucleotides may be free of unmethylated CpG motifs. Immunostimulatory oligonucleotides may be rich in pyrimidines. For example, it may contain multiple consecutive thymidine nucleotides (eg, TTTT, see ref. 136), and/or it may have , >60%, >80%, etc.) nucleotide composition. For example, it may contain multiple consecutive cytosine nucleotides (e.g., CCCC, see ref. 136), and/or it may have , >60%, >80%, etc.) the nucleotide composition of thymidine. These oligonucleotides may be free of unmethylated CpG motifs. Immunostimulatory oligonucleotides typically comprise at least 20 nucleotides. It may comprise less than 100 nucleotides.

基于免疫刺激性寡核苷酸的特别有用的佐剂称为IC-31TM[137]。因此，本发明使用的佐剂可以包含(i)和(ii)的混合物：(i)含有至少一个(优选多个)CpI基序(即，胞嘧啶与肌苷相连形成二核苷酸)的寡核苷酸(例如15-40个核苷酸)，和(ii)聚阳离子聚合物，如含有至少一个(优选多个)Lys-Arg-Lys三肽序列的寡肽(如5-20个氨基酸)。所述寡核苷酸可以是脱氧核苷酸构成的26-聚体序列5′-(IC)13-3′(SEQ ID NO：175)。所述聚阳离子聚合物可以是含有11-聚体氨基酸序列KLKLLLLLKLK(SEQ ID NO：176)的肽。寡核苷酸和聚合物可形成复合物，如参考文献138和139所述。A particularly useful adjuvant based on immunostimulatory oligonucleotides is called IC-31 ™ [137]. Thus, an adjuvant for use in the present invention may comprise a mixture of (i) and (ii): (i) an adjuvant containing at least one (preferably a plurality) of CpI motifs (i.e. cytosine linked to inosine to form a dinucleotide) Oligonucleotides (eg 15-40 nucleotides), and (ii) polycationic polymers such as oligopeptides (eg 5-20 nucleotides) containing at least one (preferably multiple) Lys-Arg-Lys tripeptide sequence amino acids). The oligonucleotide may be a 26-mer sequence 5′-(IC) 13 -3′ (SEQ ID NO: 175) composed of deoxynucleotides. The polycationic polymer may be a peptide comprising the 11-mer amino acid sequence KLKLLLLLKLK (SEQ ID NO: 176). Oligonucleotides and polymers can form complexes, as described in refs 138 and 139.

细菌ADP-核糖基化毒素及其去毒衍生物可以用作本发明的佐剂。优选所述蛋白衍生自大肠杆菌(大肠杆菌不耐热肠毒素“LT”)、霍乱菌(“CT”)或百日咳菌(“PT”)。参考文献140中描述了将脱毒的ADP-核糖基化毒素用作粘膜佐剂，参考文献141中描述了将其用作胃肠道外佐剂。所述毒素和类毒素优选全毒素形式，包含A和B亚单位。A亚单位优选含有脱毒突变；B亚单位优选不突变。佐剂优选脱毒的LT突变体如LT-K63、LT-R72和LT-G192。参考文献142-149描述ADP-核糖基化毒素及其脱毒衍生物，尤其是LT-K63和LT-R72可用作佐剂。一种有用的CT突变体是CT-E29H[150]。优选根据参考文献151中列出的ADP-核糖基化毒素的A和B亚单位的比对给氨基酸取代编号，该参考文献的全部内容通过引用全文纳入本文。Bacterial ADP-ribosylating toxins and detoxified derivatives thereof can be used as adjuvants in the present invention. Preferably the protein is derived from Escherichia coli (E. coli heat labile enterotoxin "LT"), cholera ("CT") or pertussis ("PT"). The use of detoxified ADP-ribosylating toxins as mucosal adjuvants is described in ref. 140 and as a parenteral adjuvant in ref. 141 . The toxins and toxoids are preferably in holotoxin form, comprising A and B subunits. The A subunit preferably contains detoxifying mutations; the B subunit preferably is not mutated. Adjuvants are preferably detoxified LT mutants such as LT-K63, LT-R72 and LT-G192. References 142-149 describe that ADP-ribosylating toxins and their detoxified derivatives, especially LT-K63 and LT-R72, can be used as adjuvants. A useful CT mutant is CT-E29H [150]. Amino acid substitutions are preferably numbered according to the alignment of the A and B subunits of ADP-ribosylating toxins listed in reference 151, the entire content of which is incorporated herein by reference in its entirety.

F.人免疫调节剂F. Human Immunomodulators

适合用作本发明佐剂的人免疫调节剂包括细胞因子，如白介素(如IL-1、IL-2、IL-4、IL-5、IL-6、IL-7、IL-12[152]等)[153]、干扰素(如干扰素-γ)、巨噬细胞集落刺激因子和肿瘤坏死因子。优选的免疫调节剂是IL-12。Human immunomodulators suitable for use as adjuvants in the present invention include cytokines such as interleukins (e.g. IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-12 [152] etc.) [153], interferons (such as interferon-γ), macrophage colony-stimulating factor, and tumor necrosis factor. A preferred immunomodulator is IL-12.

G.生物粘着剂和粘膜粘着剂G. Bioadhesives and mucoadhesives

生物粘着剂和粘膜粘着剂也可用作本发明的佐剂。合适的生物粘着剂包括酯化的透明质酸微球[154]或粘膜粘着剂，如聚(丙烯酸)交联衍生物、聚乙烯醇、聚乙烯吡咯烷酮、多糖和羧甲基纤维素。壳聚糖及其衍生物也可以用作本发明的佐剂[155]。Bioadhesives and mucoadhesives can also be used as adjuvants in the present invention. Suitable bioadhesives include esterified hyaluronic acid microspheres [154] or mucoadhesives such as poly(acrylic acid) crosslinked derivatives, polyvinyl alcohol, polyvinylpyrrolidone, polysaccharides, and carboxymethylcellulose. Chitosan and its derivatives can also be used as adjuvants in the present invention [155].

H.微粒H. Particles

微粒也可以用作本发明的佐剂。微粒(即直径～100nm至～150μm，优选～200nm至～30μm，最优选～500nm至～10μm的颗粒)由生物可降解和无毒的材料(例如聚(α-羟酸)、聚羟基丁酸、聚原酸酯、聚酐、聚己酸内酯等)，优选聚(丙交酯-乙交酯共聚物)形成，并任选经处理而具有带负电荷表面(例如用SDS处理)或带正电荷表面(例如用阳离子洗涤剂如CTAB处理)。Microparticles may also be used as adjuvants in the present invention. Microparticles (i.e., particles ~100 nm to ~150 μm in diameter, preferably ~200 nm to ~30 μm, most preferably ~500 nm to ~10 μm) are made of biodegradable and nontoxic materials such as poly(alpha-hydroxyacids), polyhydroxybutyrate , polyorthoesters, polyanhydrides, polycaprolactones, etc.), preferably poly(lactide-co-glycolide), optionally treated to have a negatively charged surface (for example with SDS) or Positively charged surfaces (eg treated with cationic detergents such as CTAB).

I.脂质体(参考文献82的第13和14章)I. Liposomes (chapters 13 and 14 of ref. 82)

适合用作佐剂的脂质体制剂的例子见参考文献156-158所述。Examples of liposomal formulations suitable for use as adjuvants are described in references 156-158.

J.聚氧乙烯醚和聚氧乙烯酯制剂J. Polyoxyethylene ether and polyoxyethylene ester formulations

适合用于本发明的佐剂包括聚氧乙烯醚和聚氧乙烯酯[159]。此类制剂还包括聚氧乙烯脱水山梨糖醇酯表面活性剂和辛苯聚醇[160]的组合，以及聚氧乙烯烷基醚或酯表面活性剂和至少一种另外的非离子表面活性剂如辛苯聚醇[161]的组合。优选的聚氧乙烯醚选自下组：聚氧乙烯-9-月桂醚(月桂醇聚醚9)、聚氧乙烯-9-硬脂醚、聚氧乙烯-8-硬脂醚、聚氧乙烯-4-月桂醚、聚氧乙烯-35-月桂醚和聚氧乙烯-23-月桂醚。Adjuvants suitable for use in the present invention include polyoxyethylene ethers and polyoxyethylene esters [159]. Such formulations also include combinations of polyoxyethylene sorbitan ester surfactants and octoxynol [160], as well as polyoxyethylene alkyl ether or ester surfactants and at least one additional nonionic surfactant Combinations such as octoxynol [161]. Preferred polyoxyethylene ethers are selected from the group consisting of polyoxyethylene-9-lauryl ether (laureth 9), polyoxyethylene-9-stearyl ether, polyoxyethylene-8-stearyl ether, polyoxyethylene -4-lauryl ether, polyoxyethylene-35-lauryl ether and polyoxyethylene-23-lauryl ether.

K.磷腈K. Phosphazene

可使用磷腈，如参考文献162和163中所述的聚[二(羧基苯氧基)磷腈](poly[di(carboxylatophenoxy)phosphazene]，“PCPP”。Phosphazenes, such as poly[di(carboxylatophenoxy)phosphazene], "PCPP" described in references 162 and 163, can be used.

L.胞壁酰肽L. muramyl peptide

适合用作本发明佐剂的胞壁酰肽的例子包括N-乙酰基-胞壁酰-L-苏氨酰-D-异谷酰胺(thr-MDP)、N-乙酰基-正胞壁酰-L-丙氨酰-D-异谷酰胺(正-MDP)和N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺酰-L-丙氨酸-2-(1’-2’-二棕榈酰-sn-甘油-3-羟基磷酰氧基)-乙胺MTP-PE)。Examples of muramyl peptides suitable for use as adjuvants in the present invention include N-acetyl-muramoyl-L-threonyl-D-isoglutamine (thr-MDP), N-acetyl-normuramoyl -L-alanyl-D-isoglutamine (n-MDP) and N-acetylmuramoyl-L-alanyl-D-isoglutamyl-L-alanine-2-(1' -2'-dipalmitoyl-sn-glycerol-3-hydroxyphosphoryloxy)-ethylamine (MTP-PE).

M.咪唑并喹诺酮化合物M. imidazoquinolone compounds

适合用作本发明佐剂的咪唑并喹诺酮化合物的例子包括咪喹莫特(″R-837″)[164，165]、瑞喹莫德(“R-848”)[166]，以及它们的类似物和盐(如盐酸盐)。有关免疫刺激性咪唑喹啉的其它细节可参见参考文献167-171。Examples of imidazoquinolone compounds suitable for use as adjuvants in the present invention include imiquimod ("R-837") [164, 165], resiquimod ("R-848") [166], and their Analogs and salts (such as hydrochloride). Additional details on immunostimulatory imidazoquinolines can be found in references 167-171.

M.取代的脲M. Substituted urea

用作佐剂的取代的脲包括式I、II或III的化合物，或其盐：Substituted ureas for use as adjuvants include compounds of formula I, II or III, or salts thereof:

I                II                IIII II II III

Figure BPA00001481741801381
Figure BPA00001481741801381

如参考文献172所述，例如‘ER803058’、‘ER803732’、‘ER804053’、ER804058’、‘ER804059’、‘ER804442’、‘ER804680’、‘ER804764’、ER803022或‘ER804057’，例如：As described in reference 172, for example 'ER803058', 'ER803732', 'ER804053', ER804058', 'ER804059', 'ER804442', 'ER804680', 'ER804764', ER803022 or 'ER804057', for example:

Figure BPA00001481741801382
Figure BPA00001481741801382

O.其它佐剂O. Other adjuvants

可用于本发明的其他佐剂包括：Other adjuvants that can be used in the present invention include:

●氨烷基氨基葡糖苷磷酸酯衍生物，如RC529[173，174]。• Aminoalkyl glucosaminide phosphate derivatives, such as RC529 [173, 174].

已有报道环状鸟苷酸(‘c-di-GMP’)用作金黄色葡萄球菌疫苗的佐剂[175]。Cyclic guanosine monophosphate (‘c-di-GMP’) has been reported as an adjuvant for S. aureus vaccines [175].

缩氨基硫脲化合物，如参考文献176所述的化合物。参考文献176中也描述了配制、制备和筛选活性化合物的方法。缩氨基硫脲在刺激人外周血单核细胞产生细胞因子如TNF-α方面特别有效。A thiosemicarbazone compound, such as a compound described in reference 176. Methods for formulating, preparing and screening active compounds are also described in reference 176. Thiosemicarbazones are particularly effective at stimulating the production of cytokines such as TNF-α by human peripheral blood mononuclear cells.

色胺酮化合物，如参考文献177所述的化合物。参考文献177中也描述了配制、制备和筛选活性化合物的方法。缩氨基硫脲在刺激人外周血单核细胞产生细胞因子如TNF-α方面特别有效。Tryptanthrin compounds, such as those described in reference 177. Methods for formulating, preparing and screening active compounds are also described in reference 177. Thiosemicarbazones are particularly effective at stimulating the production of cytokines such as TNF-α by human peripheral blood mononuclear cells.

●核苷类似物，如：(a)埃索他宾(Isatorabine)(ANA-245；7-硫杂-8-氧代鸟苷)及其前药：Nucleoside analogs, such as: (a) Isatorabine (ANA-245; 7-thia-8-oxoguanosine) and its prodrugs:

(b)ANA975；(c)ANA-025-1；(d)ANA380；(e)参考文献178-180所述的化合物；(b) ANA975; (c) ANA-025-1; (d) ANA380; (e) compounds described in references 178-180;

洛索立宾(Loxoribine)(7-烯丙基-8-氧代鸟苷)[181]。Loxoribine (7-allyl-8-oxoguanosine) [181].

●参考文献182所述化合物，包括：酰基哌嗪化合物、吲哚二酮化合物、四氢异喹啉(THIQ)化合物、苯并环二酮化合物、氨基氮杂乙烯基化合物、氨基苯并咪唑喹啉酮(ABIQ)化合物[183，184]、水合酞酰胺(hydrapthalamide)化合物、苯并苯基酮化合物、异

Figure BPA00001481741801392
唑化合物、固醇化合物、喹唑啉酮(quinazilinone)化合物、吡咯化合物[185]、蒽醌化合物、喹喔啉化合物、三嗪化合物、吡唑嘧啶化合物和吲哚化合物[186]。●Compounds described in reference 182, including: acyl piperazine compounds, indole diketone compounds, tetrahydroisoquinoline (THIQ) compounds, benzocyclo diketone compounds, aminoazavinyl compounds, aminobenzimidazoquine ABIQ compounds[183,184], hydrapthalamide compounds, benzophenone compounds, iso
Figure BPA00001481741801392
azole compounds, sterol compounds, quinazilinone compounds, pyrrole compounds [185], anthraquinone compounds, quinoxaline compounds, triazine compounds, pyrazolidine compounds and indole compounds [186].

●含有连接于含磷酸无环主链的脂质的化合物，如TLR4拮抗剂E5564[187，188]；● compounds containing lipids attached to a phosphate-containing acyclic backbone, such as the TLR4 antagonist E5564 [187,188];

●聚氧

Figure BPA00001481741801393
(polyoxidonium)聚合物[189，190]或其它N-氧化的聚乙烯-哌嗪衍生物；●Polyoxygen
Figure BPA00001481741801393
(polyoxidonium) polymers [189,190] or other N-oxidized polyethylene-piperazine derivatives;

●甲基肌苷5′-单磷酸酯(″MIMP″)[191]。• Methylinosine 5'-monophosphate ("MIMP") [191].

●多聚羟化吡咯双烷类化合物[192]，如下式化合物：● Polyhydroxylated pyrrolizidine compounds [192], such as compounds of the following formula:

式中，R选自：氢，直链或支链、未取代或取代、饱和或不饱和的酰基、烷基(如环烷基)、烯基、炔基和芳基，或其药学上可接受的盐或衍生物。例子包括但不限于：木麻黄(casuarine)、木麻黄-6-α-D-吡喃葡萄糖、3-表-木麻黄、7-表-木麻黄、3，7-二表-木麻黄等。In the formula, R is selected from: hydrogen, straight or branched, unsubstituted or substituted, saturated or unsaturated acyl, alkyl (such as cycloalkyl), alkenyl, alkynyl and aryl, or pharmaceutically acceptable Accepted salts or derivatives. Examples include, but are not limited to: casuarine, casuarine-6-α-D-glucopyranose, 3-epi-casuarina, 7-epi-casuarine, 3,7-di-epi-casuarine, and the like.

●CD1配体，如α-糖基神经酰胺[193-200](如α-半乳糖基神经酰胺)、含植物鞘氨醇的α-糖基神经酰胺、OCH、KRN7000[(2S，3S，4R)-1-O-(α-D-吡喃半乳糖基)-2-(N-二十六烷酰氨基)-1，3，4-十八烷三醇、CRONY-101、3″-O-硫代-半乳糖基神经酰胺等。CD1 ligands, such as α-glycosylceramide [193-200] (such as α-galactosylceramide), α-glycosylceramide containing phytosphingosine, OCH, KRN7000 [(2S, 3S, 4R)-1-O-(α-D-galactopyranosyl)-2-(N-hexacosylamino)-1,3,4-octadecanetriol, CRONY-101, 3″ -O-thio-galactosylceramide and the like.

●γ菊糖[201]或其衍生物，如阿尔加穆林(algammulin)。• Gamma inulin [201] or its derivatives, such as algammulin.

Figure BPA00001481741801401
Figure BPA00001481741801401

佐剂组合Adjuvant combination

本发明也可包含以上鉴定的一种或多种佐剂的组合。例如，可将以下佐剂组合物用于本发明：(1)皂苷和水包油乳液[202]；(2)皂苷(例如QS21)+无毒LPS衍生物(例如3dMPL)[203]；(3)皂苷(例如QS21)+无毒LPS衍生物(如3dMPL)+胆固醇；(4)皂苷(例如QS21)+3dMPL+IL-12(任选+固醇)[204]；(5)3dMPL与，例如QS21和/或水包油乳液的组合[205]；(6)SAF，含有10％角鲨烯、0.4％吐温80TM、5％普流罗尼-嵌段聚合物L121和thr-MDP，微流体化形成亚微米乳液或涡旋振荡产生粒度较大的乳液；(7)RibiTM佐剂系统(RAS)(Ribi Immunochem)，含有2％鲨烯、0.2％吐温80和一种或多种细菌细胞壁组分，所述组分选自单磷酰脂质A(MPL)、海藻糖二霉菌酸酯(TDM)或细胞壁骨架(CWS)，优选MPL+CWS(DetoxTM)；和(8)一种或多种无机盐(如铝盐)+LPS的无毒衍生物(如3dMPL)。Combinations of one or more adjuvants identified above may also be encompassed by the invention. For example, the following adjuvant compositions can be used in the present invention: (1) saponin and oil-in-water emulsion [202]; (2) saponin (such as QS21) + non-toxic LPS derivative (such as 3dMPL) [203]; ( 3) Saponin (such as QS21) + non-toxic LPS derivative (such as 3dMPL) + cholesterol; (4) Saponin (such as QS21) + 3dMPL + IL-12 (optional + sterol) [204]; (5) 3dMPL with , such as QS21 and/or a combination of oil-in-water emulsions [205]; (6) SAF containing 10% squalene, 0.4% Tween 80 TM , 5% pluronic-block polymer L121 and thr- MDP, microfluidization to form submicron emulsion or vortex oscillation to produce larger emulsion; (7) Ribi TM adjuvant system (RAS) (Ribi Immunochem), containing 2% squalene, 0.2% Tween 80 and a or a plurality of bacterial cell wall components selected from monophosphoryl lipid A (MPL), trehalose dipycolate (TDM) or cell wall skeleton (CWS), preferably MPL+CWS (Detox ™ ); and (8) One or more inorganic salts (such as aluminum salts) + non-toxic derivatives of LPS (such as 3dMPL).

用作免疫刺激剂的其它物质可参见参考文献82的第7章。See Chapter 7 of ref. 82 for other substances useful as immunostimulants.

特别优选使用氢氧化铝和/或磷酸铝佐剂，抗原通常吸附于这些盐。磷酸钙是另一种优选佐剂。其它优选的佐剂组合包括Th1和Th2佐剂的组合，如CpG和明矾或瑞喹莫德(resquimod)和明矾。可以使用磷酸铝和3dMPL的组合。Particular preference is given to using aluminum hydroxide and/or aluminum phosphate adjuvants, to which the antigen is usually adsorbed. Calcium phosphate is another preferred adjuvant. Other preferred adjuvant combinations include combinations of Th1 and Th2 adjuvants, such as CpG and alum or resquimod and alum. A combination of aluminum phosphate and 3dMPL can be used.

本发明组合物可引起细胞介导的免疫应答以及体液免疫应答。此种免疫应答优选诱导长期(如中和性)抗体和细胞介导的免疫，以便在接触肺炎球菌时迅速作出反应。The compositions of the invention can elicit a cell-mediated immune response as well as a humoral immune response. Such an immune response preferably induces long-lasting (eg, neutralizing) antibodies and cell-mediated immunity to respond rapidly upon exposure to pneumococci.

通常认为两类T细胞，CD4和CD8细胞是启动和/或增强细胞介导免疫和体液免疫所必需的。CD8 T细胞可表达CD8共同受体，通常称为细胞毒性T淋巴细胞(CTL)。CD8 T细胞能识别MHC I型分子上展示的抗原或与之相互作用。Two classes of T cells, CD4 and CD8 cells, are generally believed to be necessary for initiating and/or enhancing cell-mediated and humoral immunity. CD8 T cells express the CD8 co-receptor and are commonly referred to as cytotoxic T lymphocytes (CTLs). CD8 T cells can recognize or interact with antigens displayed on MHC class I molecules.

CD4 T细胞可表达CD4共受体，通常称为T辅助细胞。CD4 T细胞能够识别结合于MHC II型分子的抗原性肽。与MHC II型分子相互作用后，CD4细胞可分泌诸如细胞因子等因子。这些分泌的细胞因子可激活B细胞、细胞毒性T细胞、巨噬细胞和参与免疫应答的其它细胞。辅助T细胞或CD4+细胞可进一步分成功能不同的两个亚组：即，细胞因子和效应功能不同的TH1表型和TH2表型。CD4 T cells express the CD4 co-receptor and are commonly referred to as T helper cells. CD4 T cells are able to recognize antigenic peptides bound to MHC class II molecules. After interacting with MHC class II molecules, CD4 cells can secrete factors such as cytokines. These secreted cytokines activate B cells, cytotoxic T cells, macrophages and other cells involved in the immune response. Helper T cells or CD4+ cells can be further divided into two functionally distinct subgroups: namely, TH1 phenotype and TH2 phenotype with distinct cytokine and effector functions.

活化的TH1细胞能增强细胞免疫(包括抗原特异性CTL产量增加)，因而对响应胞内感染尤其有价值。激活的TH1细胞可分泌IL-2、IFN-γ和TNF-β中的一种或多种。TH1免疫应答可通过激活巨噬细胞、NK(天然杀伤细胞)细胞和CD8细胞毒性T细胞(CTL)导致局部炎性反应。通过用IL-12刺激B和T细胞的生长，TH1免疫应答也可用于放大免疫应答。TH1刺激的B细胞可分泌IgG2a。Activated TH1 cells enhance cellular immunity (including increased production of antigen-specific CTLs) and are therefore particularly valuable in response to intracellular infection. Activated TH1 cells can secrete one or more of IL-2, IFN-γ and TNF-β. A TH1 immune response can lead to a local inflammatory response by activating macrophages, NK (natural killer) cells, and CD8 cytotoxic T cells (CTL). TH1 immune responses can also be used to amplify the immune response by stimulating the growth of B and T cells with IL-12. B cells stimulated by TH1 can secrete IgG2a.

活化的TH2细胞提高抗体产量，因此对响应胞外感染有价值。活化的TH2细胞可分泌IL-4、IL-5、IL-6和IL-10中的一种或多种。TH2免疫应答可导致产生IgG1、IgE、IgA和用于未来保护的记忆B细胞。Activated TH2 cells increase antibody production and are therefore valuable in response to extracellular infection. Activated TH2 cells can secrete one or more of IL-4, IL-5, IL-6 and IL-10. A TH2 immune response can lead to the production of IgG1, IgE, IgA and memory B cells for future protection.

增强的免疫应答可包括增强的TH1免疫应答和TH2免疫应答中的一种或多种。An enhanced immune response may include one or more of an enhanced TH1 immune response and a TH2 immune response.

TH1免疫应答可包括以下一种或多种现象：CTL增加，与TH1免疫应答相关的一种或多种细胞因子(如IL-2、IFNγ和TNF-β)增加，活化巨噬细胞增加，NK活性增加，或者IgG2a产量增加。增强的TH1免疫应答优选包括IgG2a产量增加。TH1 immune response may include one or more of the following phenomena: increased CTL, increased one or more cytokines (such as IL-2, IFNγ, and TNF-β) associated with TH1 immune response, increased activated macrophages, NK Increased activity, or increased IgG2a production. The enhanced TH1 immune response preferably includes increased production of IgG2a.

可使用TH1佐剂引发TH1免疫应答。相对于不用佐剂的抗原免疫，TH1佐剂通常引起IgG2a生成水平增加。适用于本发明的TH1佐剂可包括例如，皂苷制剂、病毒体和病毒样颗粒、肠细菌脂多糖(LPS)的无毒衍生物、免疫刺激性寡核苷酸。免疫刺激性寡核苷酸，如含有CpG基序的寡核苷酸是本发明所用的优选TH1佐剂。A TH1 immune response can be elicited using a TH1 adjuvant. TH1 adjuvant generally elicited increased levels of IgG2a production relative to antigen immunization without adjuvant. TH1 adjuvants suitable for use in the present invention may include, for example, saponin preparations, virosomes and virus-like particles, non-toxic derivatives of enterobacterial lipopolysaccharide (LPS), immunostimulatory oligonucleotides. Immunostimulatory oligonucleotides, such as oligonucleotides containing CpG motifs, are preferred TH1 adjuvants for use in the present invention.

TH2免疫应答可包括以下一种或多种：与TH2免疫应答相关的一种或多种细胞因子(如IL-4、IL-5、IL-6和IL-10)增加，或者IgG1、IgE、IgA和记忆B细胞生成增加。增强的TH2免疫应答优选包括IgG1生成增加。A TH2 immune response may include one or more of the following: an increase in one or more cytokines (such as IL-4, IL-5, IL-6, and IL-10) associated with a TH2 immune response, or an increase in IgG1, IgE, IgA and memory B cell production is increased. The enhanced TH2 immune response preferably includes increased IgG1 production.

可使用TH2佐剂引发TH2免疫应答。相对于不用佐剂的抗原免疫，TH2佐剂通常引起IgG1生成水平增加。适用于本发明的TH2佐剂包括例如，含矿物质组合物、油乳液和ADP-核糖基化毒素及其脱毒衍生物。含矿物质组合物如铝盐是本发明使用的优选TH2佐剂。TH2 immune responses can be elicited using TH2 adjuvants. TH2 adjuvant generally elicits increased levels of IgG1 production relative to antigen immunization without adjuvant. TH2 adjuvants suitable for use in the present invention include, for example, mineral-containing compositions, oil emulsions, and ADP-ribosylating toxins and detoxified derivatives thereof. Mineral-containing compositions such as aluminum salts are preferred TH2 adjuvants for use in the present invention.

本发明优选包括含TH1佐剂和TH2佐剂组合的组合物。这种组合物优选引起增强的TH1和增强的TH2应答，即，IgG1和IgG2a的生产相对于不用佐剂的免疫均增加。相对于用单一佐剂的免疫(即，相对于只用TH1佐剂的免疫或只用TH2佐剂的免疫)，包含TH1和TH2佐剂组合的组合物更优选引起TH1和/或TH2免疫应答增强。The present invention preferably includes compositions comprising a combination of a TH1 adjuvant and a TH2 adjuvant. Such compositions preferably elicit enhanced TH1 and enhanced TH2 responses, ie, increased production of both IgG1 and IgG2a relative to immunization without adjuvant. Compositions comprising a combination of TH1 and TH2 adjuvants more preferably elicit a TH1 and/or TH2 immune response relative to immunization with a single adjuvant (i.e. relative to immunization with only TH1 adjuvant or only TH2 adjuvant) enhanced.

所述免疫应答可以是TH1免疫应答和TH2免疫应答中的一种或两种。免疫应答优选提供增强的TH1应答和增强的TH2应答中的一种或两种。The immune response may be one or both of TH1 immune response and TH2 immune response. The immune response preferably provides one or both of an enhanced TH1 response and an enhanced TH2 response.

增强的免疫应答可以是全身免疫应答和粘膜免疫应答中的一种或两种。该免疫应答优选提供增强的全身免疫应答和增强的粘膜免疫应答中的一种或两种。粘膜免疫应答优选为TH2免疫应答。粘膜免疫应答优选包括IgA生成增加。The enhanced immune response can be one or both of a systemic immune response and a mucosal immune response. The immune response preferably provides one or both of an enhanced systemic immune response and an enhanced mucosal immune response. The mucosal immune response is preferably a TH2 immune response. The mucosal immune response preferably includes increased IgA production.

金黄色葡萄球菌感染可影响身体的各部分，因此可将本发明组合物制备成各种形式。例如，可将所述组合物制备为液体溶液或悬浮液形式的注射剂。也可制备适合在注射前溶解或悬浮于液体运载体的固体形式(如冻干组合物或喷雾冻干组合物)。所述组合物可以制备成局部制剂，例如，油膏、乳膏或粉末。该组合物可制备成口服给药制剂，如片剂或胶囊，喷雾剂，或糖浆剂(任选调味)。所述组合物可以制备成使用细粉或喷雾的肺部给药制剂，例如吸入器。可将所述组合物制备为栓剂或阴道栓。所述组合物可以制成鼻部、耳部或眼部给药制剂，例如滴剂。组合物可以是试剂盒形式，设计成刚好在给予患者之前重建合并的组合物。此类试剂盒可包含一种或多种液体形式的抗原以及一种或多种冻干抗原。S. aureus infection can affect various parts of the body and thus the compositions of the present invention can be prepared in a variety of forms. For example, the composition can be prepared as an injection in the form of a liquid solution or suspension. Solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection (eg lyophilized or spray lyophilized compositions) can also be prepared. The compositions may be prepared in topical formulations, eg, ointments, creams or powders. The composition can be prepared as a preparation for oral administration, such as tablet or capsule, spray, or syrup (optionally flavored). The composition may be prepared for pulmonary administration using a fine powder or spray, eg, an inhaler. The composition can be prepared as a suppository or pessary. The composition may be formulated for nasal, otic or ophthalmic administration, such as drops. The compositions may be in the form of a kit designed to reconstitute the combined composition just prior to administration to a patient. Such kits may comprise one or more antigens in liquid form as well as one or more lyophilized antigens.

如果组合物要在临用前制备(例如，组分以冻干形式存在时)和以试剂盒形式存在，该试剂盒可包括两个药瓶，或者可包括一个填充好的注射器和一个药瓶，注射器内容物用于在临用前重新激活药瓶内容物。If the composition is to be prepared just before use (for example, when the components are in lyophilized form) and in kit form, the kit may include two vials, or may include a filled syringe and a vial , the contents of the syringe are used to reactivate the contents of the vial just before use.

用作疫苗的免疫原性组合物包含免疫有效量的抗原，以及需要的任何其它组分。“免疫有效量”指在一次剂量中或作为一系列剂量的一部分给予个体的治疗或预防有效用量。此用量取决于所治疗个体的健康和身体状况、年龄、所治疗个体的分类地位(如非人灵长类动物、灵长类动物等)、个体的免疫系统合成抗体的能力、所需的保护程度、疫苗配方、治疗医生对医学情况的评估和其它相关因素。预计所述用量将落入可通过常规试验测定的较宽范围内。如果组合物中包含一种以上抗原，两种抗原的剂量可以彼此相同或不同。Immunogenic compositions for use as vaccines comprise an immunologically effective amount of an antigen, and any other components required. An "immunologically effective amount" refers to a therapeutically or prophylactically effective amount administered to a subject in one dose or as part of a series of doses. This amount depends on the health and physical condition, age, taxonomic status (e.g., non-human primate, primate, etc.) of the individual to be treated, the ability of the individual's immune system to synthesize antibodies, the protection desired The extent of the vaccine, the vaccine formulation, the treating physician's assessment of the medical condition, and other relevant factors. Such amounts are expected to fall within a wide range that can be determined by routine experimentation. If more than one antigen is included in the composition, the doses of the two antigens may be the same or different from each other.

如上所述，一种组合物可包含温度保护剂，该组分可能在含佐剂的组合物(特别是含有矿物质佐剂，如铝盐的组合物)中特别有用。如参考文献206所述，可将液体温度保护剂加入水性疫苗组合物以降低其凝固点，例如将凝固点降低至0℃以下。因此，可将组合物储存在0℃以下，但在其凝固点以上以便抑制热分解。温度保护剂还允许冷冻组合物，同时保护矿物盐佐剂以免在冷冻和融化后凝聚或沉淀，还可在高温，例如40℃以上保护组合物。可混合起始水性疫苗和液体温度保护剂，从而该液体温度保护剂形成最终混合物的1-80体积％。合适的温度保护剂应该是对人安全的、易于混溶/可溶于水的、并且不应损害组合物的其他成分(如抗原和佐剂)。例子包括甘油、丙二醇和/或聚乙二醇(PEG)。合适PEG的平均分子量可以是200-20,000Da。在优选实施方式中，聚乙二醇的平均分子量可以约为300Da(‘PEG-300’)。As noted above, a composition may contain a temperature protective agent, which component may be particularly useful in adjuvanted compositions, particularly those containing mineral adjuvants such as aluminum salts. As described in reference 206, a liquid temperature protective agent can be added to an aqueous vaccine composition to lower its freezing point, eg, to lower the freezing point below 0°C. Thus, the composition may be stored below 0°C, but above its freezing point in order to inhibit thermal decomposition. Temperature protectants also allow freezing of the composition while protecting the mineral salt adjuvant from agglomeration or precipitation after freezing and thawing, and also protect the composition at elevated temperatures, eg above 40°C. The starting aqueous vaccine and the liquid thermoprotectant may be mixed such that the liquid thermoprotectant forms 1-80% by volume of the final mixture. A suitable thermoprotectant should be safe for humans, readily miscible/soluble in water, and should not damage other components of the composition (such as antigens and adjuvants). Examples include glycerin, propylene glycol and/or polyethylene glycol (PEG). A suitable PEG may have an average molecular weight of 200-20,000 Da. In a preferred embodiment, the polyethylene glycol may have an average molecular weight of about 300 Da ('PEG-300').

本发明提供一种免疫原性组合物，其包含：(i)选自第一、第二、第三或第四抗原组的一种或多种抗原；和(ii)温度保护剂。该组合物可通过混合以下组分形成：(i)包含选自第一、第二、第三或第四抗原组的一种或多种抗原的水性组合物；和(ii)温度保护剂。然后，该混合物可储存于，例如0℃以下、0-20℃、20-35℃、35-55℃或更高温度。它可以液体或冻结形式储存。该混合物可以是冻干的。或者，该组合物可通过混合以下组分形成：(i)包含选自第一、第二、第三或第四抗原组的一种或多种抗原的干燥组合物；和(ii)包含温度保护剂的液体组合物。因此，可利用组分(ii)重建组分(i)。The present invention provides an immunogenic composition comprising: (i) one or more antigens selected from the first, second, third or fourth antigen group; and (ii) a temperature protective agent. The composition may be formed by mixing: (i) an aqueous composition comprising one or more antigens selected from the first, second, third or fourth antigen groups; and (ii) a temperature protective agent. The mixture can then be stored, for example, below 0°C, 0-20°C, 20-35°C, 35-55°C or higher. It can be stored in liquid or frozen form. The mixture can be lyophilized. Alternatively, the composition may be formed by mixing: (i) a dry composition comprising one or more antigens selected from the first, second, third or fourth antigen group; and (ii) comprising a temperature Liquid compositions of protectants. Therefore, component (ii) can be used to reconstitute component (i).

治疗方法和疫苗给予Treatment and Vaccine Administration

本发明还提供了使哺乳动物产生免疫应答的方法，包括给予有效量的本发明组合物的步骤。所述免疫应答优选为保护性，优选涉及抗体和/或细胞介导的免疫。该方法可以引起加强应答。The present invention also provides a method for raising an immune response in a mammal, comprising the step of administering an effective amount of the composition of the present invention. The immune response is preferably protective, preferably involving antibody and/or cell-mediated immunity. This approach can elicit a boosted response.

本发明还提供联合用作药物的至少两种本发明抗原，以便，例如用于使哺乳动物产生免疫应答。The invention also provides at least two antigens of the invention for use in combination as a medicament, for example for raising an immune response in a mammal.

本发明也提供至少两种本发明抗原在制备使哺乳动物产生免疫应答的药物中的应用。The present invention also provides the use of at least two antigens of the present invention in the preparation of a medicament for producing an immune response in a mammal.

通过这些应用和方法在哺乳动物中产生免疫应答，能保护该哺乳动物免遭金黄色葡萄球菌感染，包括医院感染。更具体地说，可保护哺乳动物免遭皮肤感染、肺炎、脑膜炎、骨髓炎、心内膜炎、中毒性休克综合征和/或败血症。The generation of an immune response in a mammal by these uses and methods protects the mammal from S. aureus infections, including nosocomial infections. More specifically, mammals can be protected from skin infections, pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome and/or sepsis.

本发明还提供包含第一组分和第二组分的试剂盒，其中第一组分和第二组分均非上述的本发明组合物，但可混合所述第一组分和第二组分以提供上述的本发明组合物。所述试剂盒还可以包括含有下列一种或多种的第三组分：说明书、注射器或其它递送装置、佐剂或药学上可接受的配制溶液。The present invention also provides a kit comprising a first component and a second component, wherein neither the first component nor the second component is the above-mentioned composition of the invention, but the first component and the second component may be mixed to provide the composition of the invention described above. The kit can also include a third component comprising one or more of the following: instructions, a syringe or other delivery device, an adjuvant, or a pharmaceutically acceptable formulation solution.

本发明还提供了一种预填充有本发明免疫原性组合物的递送装置。The invention also provides a delivery device pre-filled with an immunogenic composition of the invention.

所述哺乳动物优选人。如果预防性使用疫苗，人优选儿童(如幼童或婴儿)；如果疫苗用于治疗用途，人优选青少年或成人。打算给予儿童的疫苗也可给予成年人，以评估(例如)其安全性、剂量、免疫原性等。可有用地按照本发明免疫的其它哺乳动物是牛、狗、马和猪。The mammal is preferably a human. If the vaccine is used prophylactically, the human is preferably a child (such as a young child or infant); if the vaccine is used for therapeutic use, the human is preferably an adolescent or an adult. Vaccines intended for children may also be administered to adults to assess, for example, their safety, dosage, immunogenicity, and the like. Other mammals which may be usefully immunized according to the invention are cattle, dogs, horses and pigs.

检测治疗性治疗的功效的一种方式包括在给予本发明组合物后监测金黄色葡萄球菌感染。一种检查预防性治疗疗效的方法包括给予组合物后监测抵御本发明组合物中抗原的全身免疫应答(如监测IgG1和IgG2a产生水平)和/或粘膜免疫应答(如监测IgA产生水平)。通常，在免疫后攻击前测定抗原特异性血清抗体应答，而在免疫后攻击后测定抗原特异性粘膜抗体应答。One way of monitoring the efficacy of therapeutic treatment involves monitoring S. aureus infection after administration of the compositions of the invention. One method of examining the efficacy of prophylactic treatment involves monitoring the systemic immune response (such as monitoring the level of IgG1 and IgG2a production) and/or the mucosal immune response (such as monitoring the level of IgA production) against the antigen in the composition of the invention after administration of the composition. Typically, antigen-specific serum antibody responses are measured prior to post-immunization challenge and antigen-specific mucosal antibody responses are measured after post-immunization challenge.

评价本发明组合物免疫原性的另一方法是重组表达蛋白，以便通过免疫印迹和/或微阵列筛查病人血清或粘膜分泌物。蛋白质和患者样品间的阳性反应表明该患者已经对受试蛋白产生免疫应答。该方法也可用于鉴定免疫显性抗原和/或抗原中的表位。Another method for assessing the immunogenicity of the compositions of the invention is to recombinantly express the protein for screening patient sera or mucosal secretions by immunoblotting and/or microarray. A positive reaction between the protein and the patient sample indicates that the patient has developed an immune response to the test protein. This method can also be used to identify immunodominant antigens and/or epitopes in antigens.

通过用疫苗组合物刺激金黄色葡萄球菌感染的动物模型，如豚鼠或小鼠可在体内测定疫苗组合物的效果。具体地说，研究金黄色葡萄球菌感染疾病有三种有用的动物模型，即：(i)小鼠脓肿模型[207]，(ii)小鼠致死性感染模型[207]和(iii)小鼠肺炎模型[208]。脓肿模型在静脉内攻击后观察小鼠肾脏中的脓肿。致死性感染模型在通过静脉内或腹膜内途径感染正常-致死剂量的金黄色葡萄球菌后观察存活小鼠数量。肺炎模型也观察存活率，但采用鼻内感染。有用的疫苗可在一种或多种这些模型中有效。例如，对于某些临床情况，可能优选抵御肺炎，而无需防止血液传播或促进调理作用；在其它情况中，主要需要防止血液传播。不同的抗原和不同的抗原组合有利于有效疫苗的不同方面。The efficacy of the vaccine composition can be determined in vivo by challenging an animal model of S. aureus infection, such as guinea pigs or mice, with the vaccine composition. Specifically, there are three useful animal models for studying S. aureus infection disease, namely: (i) mouse abscess model [207], (ii) mouse lethal infection model [207] and (iii) mouse pneumonia model [208]. Abscess Model Abscesses in mouse kidneys were observed following intravenous challenge. Lethal Infection Model The number of surviving mice was observed after infection with a normal-lethal dose of S. aureus by the intravenous or intraperitoneal route. The pneumonia model was also observed for survival, but with intranasal infection. Useful vaccines will be effective in one or more of these models. For example, for certain clinical situations, it may be preferable to protect against pneumonia without preventing blood transmission or promoting opsonization; in other cases, prevention of blood transmission is primarily desired. Different antigens and different combinations of antigens facilitate different aspects of an effective vaccine.

本发明的组合物通常直接给予患者。可通过胃肠外注射(如皮下、腹膜内、静脉内、肌肉内或注射至组织间隙)，或通过粘膜，如通过直肠、口腔(如片剂、喷雾剂)、阴道、局部、透皮或经皮、鼻内、眼、耳、肺或其它粘膜途径实现直接递送。Compositions of the invention are usually administered directly to a patient. Can be administered parenterally (eg, subcutaneously, intraperitoneally, intravenously, intramuscularly, or into an interstitial space), or via the mucosa, eg, rectally, orally (eg, tablet, spray), vaginally, topically, transdermally, or Direct delivery is achieved by transdermal, intranasal, ophthalmic, otic, pulmonary or other mucosal routes.

本发明可用于引起全身和/或粘膜免疫，优选引起增强的全身和/或粘膜免疫。The present invention can be used to elicit systemic and/or mucosal immunity, preferably enhanced systemic and/or mucosal immunity.

增强的全身和/或粘膜免疫优选表现为TH1和/或TH2免疫应答增强。增强的免疫应答优选包括IgG1和/或IgG2a和/或IgA的产量升高。Enhanced systemic and/or mucosal immunity is preferably manifested as an enhanced TH1 and/or TH2 immune response. The enhanced immune response preferably comprises increased production of IgG1 and/or IgG2a and/or IgA.

可以通过单剂量方案或多剂量方案进行给药。多剂量可以用于初次免疫方案和/或加强免疫方案。在多剂量方案中，可通过相同或不同的途径给予多个剂量，例如胃肠外初免、粘膜加强，粘膜初免、胃肠外加强等。一般以至少1周(例如约2周、约3周、约4周、约6周、约8周、约10周、约12周、约16周等)的间隔给予多个剂量。Administration can be by a single dose regimen or by a multiple dose regimen. Multiple doses can be used in the primary and/or booster regimens. In multiple dose regimens, multiple doses may be administered by the same or different routes, eg, parenteral prime, mucosal boost, mucosal prime, parenteral boost, and the like. Multiple doses are generally administered at intervals of at least 1 week (eg, about 2 weeks, about 3 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 16 weeks, etc.).

可利用本发明制备的疫苗治疗儿童和成年人。因此，人患者可以小于1岁、1-5岁、5-15岁、15-55岁或至少55岁。接受疫苗的病人优选老年人(如≥50岁，≥60岁，优选≥65岁)，年轻人(如≤5岁)，住院患者、卫生保健人员、武装机构和军事人员、孕妇、慢性病患者或免疫缺陷患者。然而，所述疫苗不仅适用于这些群体，可用于更广泛的群体。Both children and adults can be treated with vaccines prepared according to the invention. Thus, a human patient can be less than 1 year old, 1-5 years old, 5-15 years old, 15-55 years old, or at least 55 years old. Patients who receive the vaccine are preferably elderly (such as ≥50 years old, ≥60 years old, preferably ≥65 years old), young people (such as ≤5 years old), hospitalized patients, health care personnel, armed institutions and military personnel, pregnant women, patients with chronic diseases or immunocompromised patients. However, the vaccines are not only suitable for these groups, but can be used for a wider range of groups.

可将本发明产生的疫苗与其它疫苗基本上同时(在卫生保健专业人员或疫苗接种中心的同一用药咨询或访问期间)给予患者，例如与流感疫苗、麻疹疫苗、腮腺炎疫苗、风疹疫苗、MMR疫苗、水痘疫苗、MMRV疫苗、白喉疫苗、破伤风疫苗、百日咳疫苗、DTP疫苗、偶联的B型流感嗜血杆菌疫苗、脊髓灰质炎病毒灭活疫苗、乙型肝炎病毒疫苗、脑膜炎球菌偶联疫苗(如四价A-C-W135-Y疫苗)、呼吸道合胞病毒疫苗等基本上同时给药。适合共同给予的其它非葡萄球菌疫苗可包括参考文献51的第33-46行所列的一种或多种抗原。Vaccines produced according to the invention may be administered to patients substantially simultaneously (during the same medication consultation or visit with a health care professional or vaccination center) with other vaccines, such as influenza vaccine, measles vaccine, mumps vaccine, rubella vaccine, MMR vaccine Vaccines, Varicella Vaccine, MMRV Vaccine, Diphtheria Vaccine, Tetanus Vaccine, Pertussis Vaccine, DTP Vaccine, Conjugated Haemophilus Influenzae Type B Vaccine, Inactivated Polio Virus Vaccine, Hepatitis B Virus Vaccine, Meningococcal Combined vaccines (such as quadrivalent A-C-W135-Y vaccines), respiratory syncytial virus vaccines, etc. are basically administered at the same time. Other non-staphylococcal vaccines suitable for co-administration may include one or more of the antigens listed in ref. 51, lines 33-46.

核酸免疫nucleic acid immunization

上述免疫原性组合物包含金黄色葡萄球菌的多肽抗原。然而，在所有情况下，可用编码那些多肽的核酸(通常是DNA)替换多肽抗原，以得到依据核酸免疫的组合物、方法和用途。目前，核酸免疫是已开发的领域(例如，参见参考文献209-216等)。The above immunogenic composition comprises a polypeptide antigen of Staphylococcus aureus. In all cases, however, the polypeptide antigens may be replaced by nucleic acids (usually DNA) encoding those polypeptides to obtain compositions, methods and uses based on nucleic acid immunization. Nucleic acid immunization is currently an developed field (eg, see refs 209-216, etc.).

递送给患者后编码免疫原的核酸表达，然后所表达的免疫原刺激免疫系统。活性成分通常采取核酸载体形式，其包含：(i)启动子；(ii)操作性连接于启动子的免疫原编码序列；以及任选的(iii)可选择标记物。优选的载体还可包含(iv)复制起点；和(v)位于(ii)下游并与其操作性连接的转录终止子。通常，(i)和(v)为真核，(iii)和(iv)为原核。Following delivery to the patient, the nucleic acid encoding the immunogen is expressed, and the expressed immunogen then stimulates the immune system. The active ingredient typically takes the form of a nucleic acid vector comprising: (i) a promoter; (ii) an immunogen coding sequence operably linked to the promoter; and optionally (iii) a selectable marker. A preferred vector may also comprise (iv) an origin of replication; and (v) a transcription terminator downstream of and operably linked to (ii). Typically, (i) and (v) are eukaryotic and (iii) and (iv) are prokaryotic.

优选的启动子是病毒启动子，如巨细胞病毒(CMV)的启动子。除了启动子，载体还可以包含转录调节序列(如增强子)，其与启动子在功能上相互作用。优选的载体包括立即-早期CMV增强子/启动子，更优选的载体还包括CMV内含子A。启动子操作性连接于编码免疫原的下游序列，从而免疫原编码序列的表达在启动子的控制下。A preferred promoter is a viral promoter, such as that of cytomegalovirus (CMV). In addition to a promoter, a vector may also contain transcriptional regulatory sequences (such as enhancers), which functionally interact with the promoter. Preferred vectors include the immediate-early CMV enhancer/promoter, more preferred vectors also include CMV intron A. The promoter is operably linked to the downstream sequence encoding the immunogen such that expression of the immunogen coding sequence is under the control of the promoter.

如果使用标记物，优选其在微生物宿主中(如原核生物中，细菌、酵母中)具有功能。标记物优选原核选择性标记物(如在原核启动子控制下转录)。方便起见，典型的标记物为抗生素抗性基因。If a marker is used, it is preferably functional in a microbial host (eg, in prokaryotes, bacteria, yeast). The marker is preferably a prokaryotic selectable marker (eg transcription under the control of a prokaryotic promoter). For convenience, typical markers are antibiotic resistance genes.

本发明的载体优选自主复制附加型或染色体外载体，如质粒。The vectors of the invention are preferably autonomously replicating episomal or extrachromosomal vectors, such as plasmids.

本发明的载体优选包含复制起点。该复制起点优选在原核生物中有活性而在真核生物中无活性。The vectors of the present invention preferably comprise an origin of replication. The origin of replication is preferably active in prokaryotes and inactive in eukaryotes.

因此，优选的载体包含用于选择载体的原核标记物、原核复制起点以及驱动免疫原编码序列转录的真核启动子。因此，载体(a)在原核宿主中扩增并选择，但不进行多肽表达，但(b)在真核宿主中表达，但不进行扩增。这种安排对于核酸免疫载体来说是理想的。Thus, preferred vectors comprise a prokaryotic marker for vector selection, a prokaryotic origin of replication, and a eukaryotic promoter to drive transcription of the immunogen coding sequence. Thus, the vector (a) is amplified and selected in a prokaryotic host, but not subjected to polypeptide expression, but (b) is expressed in a eukaryotic host, but not amplified. This arrangement is ideal for nucleic acid immunization vectors.

本发明的载体可以在编码序列下游包含真核转录终止序列。这样能增强转录水平。如果编码序列本身不包含聚腺苷酸化序列，本发明的载体优选包含聚腺苷酸化序列。优选的聚腺苷酸化序列来自牛生长激素。The vector of the present invention may contain a eukaryotic transcription termination sequence downstream of the coding sequence. This enhances transcription levels. The vector of the invention preferably comprises a polyadenylation sequence if the coding sequence itself does not contain a polyadenylation sequence. A preferred polyadenylation sequence is from bovine somatotropin.

本发明的载体可以包含多克隆位点。The vectors of the invention may contain multiple cloning sites.

除免疫原和标记物的编码序列外，载体可以包含第二真核编码序列。载体还可在所述第二序列上游包含IRES，以便从与该免疫原相同转录物翻译第二真核多肽。或者，免疫原编码序列可以在IRES的下游。In addition to the coding sequences for the immunogen and marker, the vector may contain a second eukaryotic coding sequence. The vector may also comprise an IRES upstream of said second sequence, so that the second eukaryotic polypeptide is translated from the same transcript as the immunogen. Alternatively, the immunogen coding sequence can be downstream of the IRES.

本发明的载体可以包含非甲基化CpG基序，如非甲基化DNA序列，它们都在鸟苷之前有一个胞嘧啶，侧接有两个5′嘌呤和两个3′嘧啶。已证明非甲基化形式的这些DNA基序是几类免疫细胞的强效刺激物。The vectors of the invention may contain unmethylated CpG motifs, such as unmethylated DNA sequences, all of which have a cytosine preceding the guanosine flanked by two 5'purines and two 3'pyrimidines. These DNA motifs in unmethylated form have been shown to be potent stimulators of several types of immune cells.

载体可以靶向方式递送。受体介导的DNA递送技术描述于，例如参考文献217-222。在基因治疗方案中，以约100ng-200mg DNA的范围局部给予包含核酸的治疗性组合物。在基因治疗方案中也能使用浓度范围是约500ng-50mg，约1μg-2mg，约5μg-500μg以及约20μg-100μg DNA。各种因素，例如作用方法(如增强或抑制编码基因产物的水平)以及转化和表达效率是影响最终效果所需剂量的考虑因素。如果需要在更大面积组织上的更强表达，可能需要更大量的载体或在连续给药方案中重复给予相同量，或对不同相邻或附近组织部分多次给药，以达到阳性治疗效果。在所有情况下，采用临床试验中的常规实验方法确定最优治疗效果的具体范围。Vectors can be delivered in a targeted manner. Receptor-mediated DNA delivery techniques are described, eg, in refs 217-222. In a gene therapy regimen, a therapeutic composition comprising a nucleic acid is administered topically in the range of about 100 ng-200 mg of DNA. Concentration ranges of about 500 ng-50 mg, about 1 μg-2 mg, about 5 μg-500 μg, and about 20 μg-100 μg DNA can also be used in gene therapy regimens. Factors such as the method of action (eg, enhancing or inhibiting the level of the encoded gene product) and the efficiency of transformation and expression are considerations in the dosage required to affect the ultimate effect. If stronger expression over a larger area of tissue is desired, larger amounts of vector or repeated administration of the same amount in a sequential dosing regimen, or multiple doses to different adjacent or nearby tissue segments may be required to achieve a positive therapeutic effect . In all cases, the specific range for optimal therapeutic effect will be determined using routine experimental methods in clinical trials.

可用基因递送运载体来递送载体。基因递送运载体可以是病毒或非病毒来源(通常参见参考文献223-226)。The vector can be delivered using a gene delivery vehicle. Gene delivery vehicles can be of viral or non-viral origin (see generally refs. 223-226).

本领域熟知用于递送所需核酸并在所需细胞中表达的病毒载体。示例性的病毒载体包括但不限于：重组逆转录病毒(例如参考文献227-237)，α病毒载体(如辛德毕斯病毒载体、西门利克森林病毒(ATCC VR-67；ATCCVR-1247)、罗斯河病毒(ATCC VR-373；ATCC VR-1246)和委内瑞拉马脑炎病毒(ATCC VR-923；ATCC VR-1250；ATCC VR 1249；ATCC VR-532)；还可以使用这些病毒的杂交体或嵌合体)、痘病毒载体(如牛痘、鸟痘、金丝雀痘、改性的安卡拉牛痘等)、腺病毒载体和腺伴随病毒(AAV)载体(例如参见参考文献238-243)。还可采用给予与杀伤的腺病毒连接的DNA[244]。Viral vectors are well known in the art for delivery of desired nucleic acids and expression in desired cells. Exemplary viral vectors include, but are not limited to: recombinant retroviruses (e.g. refs 227-237), alphavirus vectors (e.g. Sindbis virus vectors, Semenlik Forest virus (ATCC VR-67; ATCC VR-1247), Ross River Viruses (ATCC VR-373; ATCC VR-1246) and Venezuelan equine encephalitis virus (ATCC VR-923; ATCC VR-1250; ATCC VR 1249; ATCC VR-532); hybrids or chimeras of these viruses can also be used ), poxvirus vectors (such as vaccinia, fowlpox, canarypox, modified vaccinia Ankara, etc.), adenovirus vectors and adeno-associated virus (AAV) vectors (see eg refs 238-243). Administration of DNA linked to a killed adenovirus can also be used [244].

还能使用非病毒递送载体和方法，包括但不限于：连接或不连接于杀杀伤腺病毒的聚阳离子凝集DNA[如244]，配体连接的DNA[245]，真核细胞递送运载体细胞[如参考文献246-250]和核电荷中和或与细胞膜融合。还可利用裸DNA。参考文献251和252中描述了引入裸DNA的示例性方法。参考文献253-257描述了可用作递送载体的脂质体(例如，免疫脂质体)。参考文献258和259中描述了其它方法。Non-viral delivery vehicles and methods can also be used, including but not limited to: polycationic condensed DNA linked or not linked to a killer adenovirus [e.g. 244], ligand-linked DNA [245], eukaryotic cell delivery vehicles [eg refs 246-250] and nuclear charge neutralization or fusion with cell membranes. Naked DNA can also be utilized. Exemplary methods for introducing naked DNA are described in references 251 and 252. References 253-257 describe liposomes (eg, immunoliposomes) that can be used as delivery vehicles. Other methods are described in refs 258 and 259.

其它适用的非病毒递送包括机械递送系统，如参考文献259所述的方法。此外，可通过光聚合水凝胶材料沉积或使用离子辐射递送此编码序列和其表达产物[如参考文献260和261]。可用于递送编码序列的其它常规基因递送方法包括例如，使用手持式基因传递颗粒枪[262]或使用离子辐射激活转移的基因[260和261]。Other suitable non-viral delivery systems include mechanical delivery systems, such as those described in reference 259. Furthermore, this coding sequence and its expression products can be delivered by deposition of photopolymerizable hydrogel materials or using ionizing radiation [eg refs 260 and 261]. Other conventional gene delivery methods that can be used to deliver coding sequences include, for example, the use of hand-held gene delivery particle guns [262] or the use of ionizing radiation to activate transferred genes [260 and 261].

使用PLG(乙交酯-丙交酯共聚物)微粒递送DNA是尤其优选的方法，如通过吸附于微粒，微粒经任选处理表面带负电(如用SDS处理)或带正电(如用阳离子洗涤剂如CTAB处理)。The use of PLG (glycolide-lactide copolymer) microparticles is a particularly preferred method for DNA delivery, e.g. by adsorption to microparticles, which are optionally surface treated negatively (e.g. with SDS) or positively (e.g. with cationic Detergents such as CTAB treatment).

表皮葡萄球菌(S.epidermidis)Staphylococcus epidermidis (S. epidermidis)

虽然本发明将注意力集中在金黄色葡萄球菌，但本发明人也意识到sta006和sta011抗原与表皮葡萄球菌有同源性。例如，SEQ ID NO：234是表皮葡萄球菌菌株M23864：W1的‘铁(Fe+3)ABC超家族ATP结合盒转运体，结合蛋白’，与SEQ ID NO：42(sta006)有73％相同性，SEQ ID NO：235是表皮葡萄球菌菌株RP62A的‘推定脂蛋白’，与SEQ ID NO：47(sta011)有67％相同性。While the present invention focuses on S. aureus, the inventors also realized that the sta006 and sta011 antigens have homology to S. epidermidis. For example, SEQ ID NO: 234 is the 'Iron (Fe+3) ABC superfamily ATP-binding cassette transporter, binding protein' of Staphylococcus epidermidis strain M23864:W1, 73% identical to SEQ ID NO: 42 (sta006) , SEQ ID NO: 235 is the 'putative lipoprotein' of Staphylococcus epidermidis strain RP62A, 67% identical to SEQ ID NO: 47 (sta011).

表皮葡萄球菌通常存在于人皮肤上，有时可致病。其感染通常与医疗装置，例如导管相关，并且是医院感染的原因。本文公开的sta006和sta011抵御金黄色葡萄球菌的结果提示表皮葡萄球菌中的同源性蛋白可用作免疫以便抵御该病毒。Staphylococcus epidermidis is commonly found on human skin and can sometimes cause disease. Its infection is often associated with medical devices, such as catheters, and is the cause of nosocomial infections. The results disclosed herein for sta006 and sta011 against S. aureus suggest that homologous proteins in S. epidermidis can be used for immunization against this virus.

本发明提供免疫原性组合物，其包含：The invention provides immunogenic compositions comprising:

(i)包含某种氨基酸序列的多肽，所述氨基酸序列：(a)与SEQ ID NO：234具有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：234的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)；(i) a polypeptide comprising an amino acid sequence: (a) 50% or more identical to SEQ ID NO: 234 (e.g., 60%, 65%, 70%, 75%, 80% , 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or higher); and/or (b) comprising SEQ ID NO: A fragment of at least 'n' contiguous amino acids of 234, wherein 'n' is 7 or higher (e.g. 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60 , 70, 80, 90, 100, 150, 200, 250 or higher);

和/或and / or

(ii)包含某种氨基酸序列的多肽，所述氨基酸序列：(a)与SEQ ID NO：235具有50％或更高相同性(例如，60％、65％、70％、75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或更高)；和/或(b)包含SEQ ID NO：235的至少‘n’个毗连氨基酸的片段，其中‘n’是7或更高(例如8、10、12、14、16、18、20、25、30、35、40、50、60、70、80、90、100、150、200、250或更高)。(ii) a polypeptide comprising an amino acid sequence: (a) 50% or more identical to SEQ ID NO: 235 (e.g., 60%, 65%, 70%, 75%, 80% , 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or higher); and/or (b) comprising SEQ ID NO: A fragment of at least 'n' contiguous amino acids of 235, wherein 'n' is 7 or higher (e.g. 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60 , 70, 80, 90, 100, 150, 200, 250 or higher).

该组合物还可包含佐剂。这些组合物尤其可用于免疫哺乳动物(包括人)以便抵御表皮葡萄球菌感染。The composition may also contain an adjuvant. These compositions are especially useful for immunizing mammals, including humans, against S. epidermidis infection.

(b)的优选片段分别包含来自SEQ ID NO：234或235的表位。其它优选片段缺少SEQ ID NO：234/235的C末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)和/或SEQ ID NO：234/235的N末端的一个或多个氨基酸(如1、2、3、4、5、6、7、8、9、10、15、20、25或更多个)，而保留SEQ ID NO：234/235的至少一个表位。Preferred fragments of (b) comprise an epitope from SEQ ID NO: 234 or 235, respectively. Other preferred fragments lack one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the C-terminus of SEQ ID NO: 234/235 ) and/or one or more amino acids (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) at the N-terminal of SEQ ID NO: 234/235 multiple), while retaining at least one epitope of SEQ ID NO: 234/235.

更泛泛地说，本发明提供任何葡萄球菌种类的sta006和/或sta011同源物在免疫哺乳动物以便抵御该种类中的应用。More generally, the invention provides the use of sta006 and/or sta011 homologues of any Staphylococcus species for immunizing a mammal against that species.

抗体Antibody

抗金黄色葡萄球菌抗原的抗体可用于被动免疫。因此，本发明提供第一、第二、第三或第四抗原组中抗原的特异性抗体。本发明还提供此类抗体在治疗中的应用。本发明还提供此类抗体在药物制造中的应用。本发明还提供治疗哺乳动物的方法，包括给予有效量的本发明抗体的步骤。如上文免疫原性组合物所述，这些方法和应用能够保护哺乳动物免遭金黄色葡萄球菌感染。Antibodies against S. aureus antigens can be used for passive immunization. Accordingly, the present invention provides antibodies specific for antigens in the first, second, third or fourth antigen group. The invention also provides the use of such antibodies in therapy. The present invention also provides the use of such antibodies in the manufacture of medicines. The invention also provides a method of treating a mammal comprising the step of administering an effective amount of an antibody of the invention. These methods and uses are capable of protecting mammals from S. aureus infection, as described above for the immunogenic compositions.

术语“抗体”包括完整的免疫球蛋白分子及其能结合抗原的片段。它们包括杂交(嵌合)抗体分子[263，264]；F(ab′)2和F(ab)片段和Fv分子；非共价异源二聚体[265，266]；单链Fv分子(sFv)[267]；二聚和三聚抗体片段构建物；微型抗体[268，269]；人源化抗体分子[270-272]；和获自此类分子的任何功能片段，以及通过非常规工艺，如噬菌体展示获得的抗体。所述抗体优选单克隆抗体。获取单克隆抗体的方法为本领域熟知。优选人源化或完全人抗体。The term "antibody" includes intact immunoglobulin molecules and fragments thereof that are capable of binding antigen. They include hybrid (chimeric) antibody molecules [263,264]; F(ab')2 and F(ab) fragments and Fv molecules; non-covalent heterodimers [265,266]; single-chain Fv molecules ( sFv)[267]; dimeric and trimeric antibody fragment constructs; minibodies [268,269]; humanized antibody molecules [270-272]; Processes such as phage display to obtain antibodies. The antibody is preferably a monoclonal antibody. Methods for obtaining monoclonal antibodies are well known in the art. Humanized or fully human antibodies are preferred.

概述overview

除非另有说明，本发明的实施将采用常规的化学、生物化学、分子生物学、免疫学和药理学方法，这些方法是所述领域技术人员已知的。这些技术在文献中已有充分描述。参见例如，参考文献273-280等。The practice of the present invention will employ, unless otherwise indicated, conventional methods of chemistry, biochemistry, molecular biology, immunology and pharmacology, which are known to those skilled in the art. Such techniques are fully described in the literature. See, eg, refs. 273-280 et al.

上文使用“GI”编号。GI编号，或者“基因信息识别符”(GenInfo Identifier)是NCBI将序列加入其数据库时，连续对每一序列记录指定的一串数字。GI编号与序列记录登录号不相似。序列更新(如纠正或加入更多注释或信息)后，将接受新GI编号。因此，与给定GI编号相关的序列是不变的。"GI" numbers are used above. GI number, or "GenInfo Identifier" (GenInfo Identifier) is a string of numbers assigned to each sequence record continuously when NCBI adds the sequence to its database. GI numbers are not similar to sequence record accession numbers. New GI numbers will be accepted after sequence updates (eg corrections or addition of additional notes or information). Therefore, the sequence associated with a given GI number is invariant.

如果本发明涉及“表位”，该表位可以是B细胞表位和/或T细胞表位。可凭经验确定此类表位(如利用PEPSCAN[281，282]或相似方法)，或可预测这些表位(如利用Jameson-Wolf抗原性指数[283]、基于矩阵的方法[284]、MAPITOPE[285]、TEPITOPE[286，287]、神经网络[288]、OptiMer & EpiMer[289，290]、ADEPT[291]、Tsites[292]、亲水性[293]、抗原性指数[294]、或参考文献295-299中所述的方法等)。表位是抗体或T细胞受体的抗原结合位点识别并结合的抗原的某部分，也称作“抗原决定簇”。If the present invention refers to an "epitope", this epitope may be a B-cell epitope and/or a T-cell epitope. Such epitopes can be determined empirically (eg, using PEPSCAN [281, 282] or similar methods), or can be predicted (eg, using the Jameson-Wolf Antigenicity Index [283], matrix-based methods [284], MAPITOPE [285], TEPITOPE [286, 287], neural network [288], OptiMer & EpiMer [289, 290], ADEPT [291], Tsites [292], hydrophilicity [293], antigenicity index [294], or methods described in refs 295-299, etc.). An epitope is a certain portion of an antigen that is recognized and bound by the antigen binding site of an antibody or T cell receptor, also referred to as an "antigenic determinant".

如果省去抗原“结构域”，可包括省去信号肽、胞质结构域、跨膜结构域、胞外结构域等。If the antigen "domain" is omitted, it may include the omission of signal peptide, cytoplasmic domain, transmembrane domain, extracellular domain, etc.

术语“包含”包括“包括”以及“由...组成”，例如，“包含”X的组合物可以仅由X组成或可以包含其它物质，例如X+Y。The term "comprising" includes "including" as well as "consisting of", eg, a composition "comprising" X may consist of X alone or may contain other substances, eg X+Y.

与数值x相关的术语“约”是任选的并表示例如x±10％。The term "about" in relation to a value x is optional and means, for example, x ± 10%.

述及两个氨基酸序列间的序列相同性百分数表示进行比对时，所比较的两条序列中相同氨基酸的百分数。可利用本领域已知的软件程序，例如参考文献300的7.7.18部分所描述的那些进行比对并确定同源性百分数或序列相同性百分数。优选通过Smith-Waterman同源性检索算法进行比对，该算法使用仿射空位检索，其中空位开放罚分12，空位延伸罚分2，BLOSUM矩阵为62。参考文献301中公开了Smith-Waterman同源性检索算法。Reference to a percent sequence identity between two amino acid sequences means, when aligned, the percent of identical amino acids in the two sequences being compared. Alignment and determination of percent homology or percent sequence identity can be performed using software programs known in the art, such as those described in section 7.7.18 of ref. 300. Alignment is preferably performed by the Smith-Waterman homology search algorithm using an affine gap search with a gap opening penalty of 12, a gap extension penalty of 2, and a BLOSUM matrix of 62. The Smith-Waterman homology search algorithm is disclosed in reference 301.

附图简述Brief description of the drawings

图1显示已用所示抗原免疫的小鼠在攻击后的细菌计数(Log cfu/ml)。Figure 1 shows the bacterial counts (Log cfu/ml) after challenge in mice that had been immunized with the indicated antigens.

图2-4显示已用各种抗原混合物免疫的小鼠在攻击后的14天期间的存活率(％)。在图2中，14天时，SA-10-a的6组从上到下是组(i)、(iii)和(iv)一起、(ii)、IsdB、然后是阴性对照。在图3中，14天时，SA-10-a的6组从上到下是组(i)、(iii)和(iv)一起、(ii)、IsdB、然后是阴性对照。在图3中，14天时，SA-10-b的6组从上到下是组(iii)、(i)、(iv)、(ii)和IsdB一起、然后是阴性对照。在图4中，14天时，SA-14的6组从上到下是组(iv)、(ii)、(i)、(iii)、阴性对照和IsdB。Figures 2-4 show the survival rate (%) during the 14 days post-challenge of mice that had been immunized with various antigen mixtures. In Figure 2, at 14 days, the 6 groups of SA-10-a from top to bottom are groups (i), (iii) and (iv) together, (ii), IsdB, and then the negative control. In Figure 3, at 14 days, the 6 groups of SA-10-a from top to bottom are groups (i), (iii) and (iv) together, (ii), IsdB, and then the negative control. In Figure 3, at 14 days, the 6 groups of SA-10-b from top to bottom are groups (iii), (i), (iv), (ii) together with IsdB, and then the negative control. In Figure 4, at 14 days, the 6 groups of SA-14 from top to bottom are group (iv), (ii), (i), (iii), negative control and IsdB.

图5显示攻击已用各种组合物(PBS阴性对照；IsdB抗原；及本发明的“Combo-1”和“Combo-2”抗原组合)免疫的小鼠后，从4个不同实验收集的小鼠存活数据。各标志显示各小鼠的存活持续时间；各组的水平棒(horizontalbar)显示中值存活持续时间；百分数是攻击后14天的存活率；顶部的p值是各组之间中值存活持续时间的t-检验比较。Fig. 5 shows the mice collected from 4 different experiments after challenging mice immunized with various compositions (PBS negative control; IsdB antigen; and "Combo-1" and "Combo-2" antigen combinations of the present invention). Rat survival data. Each symbol shows the duration of survival for each mouse; the horizontal bar for each group shows the median duration of survival; the percentage is the survival rate at 14 days after challenge; the p-value at the top is the median duration of survival between the groups t-test comparisons.

图6显示脓肿模型中，用9x106cfu的Newman菌株感染后，小鼠肾脏中菌落形成单位(cfu)的数量。水平棒是每组的平均值，各组下的数字是相对于PBS对照组的降低值的对数。Figure 6 shows the number of colony forming units (cfu) in mouse kidneys after infection with 9x106 cfu of Newman strain in an abscess model. Horizontal bars are mean values for each group and numbers below each group are logarithmic reductions relative to the PBS control group.

图7显示脓肿模型实验中小鼠肾脏中的细菌计数(log CFU/ml)。用以下菌株攻击小鼠：(A)MW2；(B)LAC；(C)Staph19；或(D)MU50。各点是各动物，棒显示每组的中值计数。如x-轴标记所示免疫小鼠。Figure 7 shows the bacterial count (log CFU/ml) in the mouse kidney in the abscess model experiment. Mice were challenged with the following strains: (A) MW2; (B) LAC; (C) Staph19; or (D) MU50. Dots are individual animals, bars show median counts for each group. Mice were immunized as indicated by x-axis labels.

图8显示有浓度增加的Ca++离子存在下Sta011寡聚物的形成。数值表示mM浓度，*表示有50mM EDTA存在。Figure 8 shows the formation of Sta011 oligomers in the presence of increasing concentrations of Ca ++ ions. Values represent mM concentrations, * indicates the presence of 50 mM EDTA.

图9显示抵御(A)EsxAB、(B)Sta006、(C)Hla-H35L、(D)Sta011的IgG滴度。各图具有3组，每组一对柱。每对中右侧的柱显示免疫前IgG，左侧柱显示免疫后IgG。3组是用于免疫的组合物，从左到右是：仅有佐剂的阴性对照；Combo1组合；和仅有相关抗原。Figure 9 shows IgG titers against (A) EsxAB, (B) Sta006, (C) Hla-H35L, (D) Sta011. Each graph has 3 sets, each with a pair of bars. The right column in each pair shows pre-immune IgG and the left column shows post-immune IgG. Group 3 are the compositions used for immunization, from left to right: negative control with adjuvant only; Combo1 combination; and relevant antigen only.

图10显示用所示菌株攻击后小鼠中的细菌计数值(log CFU/ml)。各点是各小鼠，棒显示中值CFU。IsdB和Combo柱下的P值是相对于仅有佐剂对照的比较值。Figure 10 shows the bacterial counts (log CFU/ml) in mice following challenge with the indicated strains. Dots are individual mice, bars show median CFU. P values under the IsdB and Combo columns are compared to the adjuvant only control.

图11显示用Newman菌株攻击后小鼠的脓肿面积(mm2)。Figure 11 shows the abscess area (mm 2 ) of mice after challenge with Newman strain.

图12显示用4种不同菌株攻击后的小鼠存活天数：Newman(○)、ST-80(□)、USA300-FPR3757(△)或USA300-Lac(x)菌株。各点是各小鼠，棒显示中值存活时间，顶部数值显示15天后的动物存活％。小鼠接受仅氢氧化铝佐剂、IsdB或对照。Figure 12 shows the survival days of mice after challenge with 4 different strains: Newman (◯), ST-80 (□), USA300-FPR3757 (△) or USA300-Lac (x) strains. Dots are individual mice, bars show median survival time and top numbers show % survival of animals after 15 days. Mice received aluminum hydroxide adjuvant alone, IsdB or control.

图13显示攻击后小鼠的中值存活时间(天)。用X-轴所示抗原免疫小鼠。各点是各小鼠，棒显示中值存活时间。顶部数值显示15天后的动物存活％。Figure 13 shows the median survival time (days) of mice after challenge. Mice were immunized with antigens indicated on the X-axis. Dots are individual mice, bars show median survival time. Top numbers show % animal survival after 15 days.

本发明的实施方式Embodiments of the present invention

抗原选择antigen selection

根据各种标准选择金黄色葡萄球菌蛋白用作疫苗组分。S. aureus proteins were selected for use as vaccine components according to various criteria.

IsdA是参与铁摄取的表面蛋白。其可在金黄色葡萄球菌的完整细胞裂解物和细胞壁组分的免疫印迹中检测，分子量高(＞250kDa)。此外，标记的抗-IsdA抗体显示胞外结构。可在各种生长和感染条件下观察到这些结构，包括铁阳性条件(其中据报道IsdA表达受抑制)。所述结构具有最多4μm长的尾，典型的取向平行于哺乳动物细胞表面。观察到分离的IsdA-阳性结构粘附于上皮细胞表面，但丧失细胞连接定位。上皮/细菌相互作用可刺激这些结构的表达。此外，本发明人发现IsdA在不同菌株之间保守性良好(在测试的36种菌株中均存在；参见下文)，因而对流行菌株的广泛群体赋予保护作用。铁摄取对于毒力至关重要，因此，该蛋白质在细菌生命周期的病理学阶段可能为免疫攻击所用。本发明人发现该蛋白质对人细胞无细胞毒性(参见下文)。该蛋白质还能合理地良好吸附于氢氧化铝(参见下文)，从而可用于稳定的制剂以便递送给人。其可用于提供免疫应答以防止细菌的血液传播。IsdA is a surface protein involved in iron uptake. It is detectable in immunoblots of whole cell lysates and cell wall fractions of S. aureus and is of high molecular weight (>250 kDa). In addition, labeled anti-IsdA antibodies showed extracellular structures. These structures can be observed under various growth and infection conditions, including iron positive conditions (where IsdA expression is reported to be suppressed). The structures have tails up to 4 μm long, typically oriented parallel to the mammalian cell surface. Isolated IsdA-positive structures were observed to adhere to the surface of epithelial cells but lose cell junctional localization. Epithelial/bacterial interactions can stimulate the expression of these constructs. Furthermore, the inventors found that IsdA is well conserved across strains (present in all 36 strains tested; see below), thus conferring protection on a broad population of circulating strains. Iron uptake is critical for virulence, so this protein may be used for immune attack during pathological stages of the bacterial life cycle. The inventors found that this protein was not cytotoxic to human cells (see below). The protein also adsorbs reasonably well to aluminum hydroxide (see below) and thus can be used in stable formulations for delivery to humans. It can be used to provide an immune response to prevent blood spread of bacteria.

EsxA和EsxB是小的酸性二聚分泌型蛋白。本发明人发现EsxA在不同菌株之间高度保守(在测试的36种菌株中均存在；参见下文)，而EsxB存在于36种菌株中的25种。这些蛋白质参与感染的维持，因此在细菌生命周期的病理学阶段可能为免疫攻击所用。本发明人发现EsxA和EsxB的融合体(‘EsxAB’)对人细胞无细胞毒性(参见下文)。其还能良好吸附于氢氧化铝(参见下文)，从而可用于稳定的制剂以便递送给人。因此，这些抗原可用于提供免疫应答以防止细菌的血液传播。EsxA and EsxB are small acidic dimeric secreted proteins. The inventors found that EsxA is highly conserved among the different strains (present in all 36 strains tested; see below), whereas EsxB is present in 25 of the 36 strains. These proteins are involved in the maintenance of infection and thus may be available for immune attack during pathological stages of the bacterial life cycle. The inventors found that a fusion of EsxA and EsxB ('EsxAB') was not cytotoxic to human cells (see below). It also adsorbs well to aluminum hydroxide (see below), allowing for stable formulations for delivery to humans. Therefore, these antigens can be used to provide an immune response to prevent blood spread of bacteria.

Hla是成孔的分泌型毒素。该蛋白在不同菌株之间保守性良好(在测试的36种菌株中均存在；参见下文)，因此对流行菌株的广泛群体赋予保护作用。其是重要的毒力因子，因此在细菌生命周期的病理学阶段可能为免疫攻击所用。其对人细胞无细胞毒性(参见下文)。该蛋白质能合理地良好吸附于氢氧化铝(参见下文)，从而可用于稳定的制剂以便递送给人。其可用于提供免疫应答以防止肺炎。HIa is a pore-forming secreted toxin. This protein is well conserved across strains (present in all 36 strains tested; see below), thus conferring protection to a broad population of circulating strains. It is an important virulence factor and thus may be used for immune attack during the pathological stages of the bacterial life cycle. It is non-cytotoxic to human cells (see below). The protein adsorbs reasonably well to aluminum hydroxide (see below) and thus can be used in stable formulations for delivery to humans. It can be used to provide an immune response to prevent pneumonia.

Spa是参与Fc结合的表面蛋白。本发明人发现该蛋白在不同菌株之间保守性良好(在测试的36种菌株中均存在)，因此对流行菌株的广泛群体赋予保护作用。其对于毒力至关重要，因此在细菌生命周期的病理学阶段可能为免疫攻击所用。该蛋白质还能合理地良好吸附于氢氧化铝(参见下文)，从而可用于稳定的制剂以便递送给人。其可用于提供免疫应答以防止细菌的血液传播。Spa is a surface protein involved in Fc binding. The inventors found that this protein is well conserved among different strains (present in all 36 strains tested), thus conferring protection to a broad population of circulating strains. It is essential for virulence and thus may be used for immune attack during pathological stages of the bacterial life cycle. The protein also adsorbs reasonably well to aluminum hydroxide (see below) and thus can be used in stable formulations for delivery to humans. It can be used to provide an immune response to prevent blood spread of bacteria.

Sta006(也称为FhuD2)是参与铁摄取的表面蛋白。本发明人发现该蛋白在不同菌株之间保守性良好(在测试的36种菌株中均存在)，因此对流行菌株的广泛群体赋予保护作用。本发明人发现该蛋白对人细胞无细胞毒性(参见下文)。该蛋白质还能合理地良好吸附于氢氧化铝(参见下文)，从而可用于稳定的制剂以便递送给人。其可用于提供免疫应答以防止细菌的血液传播。Sta006 (also known as FhuD2) is a surface protein involved in iron uptake. The inventors found that this protein is well conserved among different strains (present in all 36 strains tested), thus conferring protection to a broad population of circulating strains. The inventors have found that this protein is not cytotoxic to human cells (see below). The protein also adsorbs reasonably well to aluminum hydroxide (see below) and thus can be used in stable formulations for delivery to humans. It can be used to provide an immune response to prevent blood spread of bacteria.

Sta011是表面脂蛋白。本发明人发现该蛋白在不同菌株之间保守性良好(在测试的36种菌株中均存在)，因此对流行菌株的广泛群体赋予保护作用。本发明人发现该蛋白对人细胞无细胞毒性(参见下文)。该蛋白质还能合理地良好吸附于氢氧化铝(参见下文)，从而可用于稳定的制剂以便递送给人。其可用于提供免疫应答以防止细菌的血液传播。该蛋白质显示在有Ca++离子，而没有Mg++离子存在下可组装成寡聚物(参见图8)。这些实验利用5μg重组的无标签Sta011，37℃与浓度从0.5到50mM增加的CaCl2温育25分钟，然后利用透明的非变性凝胶通过凝胶电泳分析。从2mM Ca++开始，特别是＞5mM时泳动率变动(表明寡聚化)明显。这些水平与血液Ca++浓度约1.2mM、血清浓度约11mM和乳浓度约32mM相当。EDTA揭示该变动。Sta011 is a surface lipoprotein. The inventors found that this protein is well conserved among different strains (present in all 36 strains tested), thus conferring protection to a broad population of circulating strains. The inventors have found that this protein is not cytotoxic to human cells (see below). The protein also adsorbs reasonably well to aluminum hydroxide (see below) and thus can be used in stable formulations for delivery to humans. It can be used to provide an immune response to prevent blood spread of bacteria. The protein was shown to assemble into oligomers in the presence of Ca ++ ions, but not Mg ++ ions (see Figure 8). These experiments utilized 5 μg of recombinant untagged Sta011 incubated for 25 minutes at 37°C with increasing concentrations of CaCl2 from 0.5 to 50 mM and then analyzed by gel electrophoresis using clear, non-denaturing gels. Starting at 2 mM Ca ++ , a shift in mobility (indicating oligomerization) is evident especially at >5 mM. These levels are comparable to blood Ca ++ concentrations of approximately 1.2 mM, serum concentrations of approximately 11 mM, and milk concentrations of approximately 32 mM. EDTA reveals this change.

分泌蛋白的表面消化[302]和/或分析揭示以下的肽片段：ClfA、ClfB、coA、eap、ebhA、ebpS、efb、emp、FnBA、FnBB、hla、IsdA、IsdB、lsdH、ukD、lukS、sdrD、sdrE、sasB、sasD、sasF、spa、sta001、sta002、sta003、sta004、sta005、sta006、sta007、sta008、sta009、sta010、sta011、sta019、sta023、sta024、sta028、sta036、sta040、sta049、sta050、sta054、sta057、sta064、sta065、sta073、sta095、sta096、sta098、sta100、sta101、sta102、sta103、sta105、sta107、sta108、sta109、sta111、sta112、sta113、sta115、sta116、sta117、sta118、sta120、NW_06、NW_07、NW_08、NW_09和NW_10，例如SEQ ID NO：228和229鉴定为sta019的片段。Surface digestion [302] and/or analysis of secreted proteins revealed the following peptide fragments: CIfA, CIfB, coA, eap, ebhA, ebpS, efb, emp, FnBA, FnBB, hla, IsdA, IsdB, lsdH, ukD, lukS, sdrD, sdrE, sasB, sasD, sasF, spa, sta001, sta002, sta003, sta004, sta005, sta006, sta007, sta008, sta009, sta010, sta011, sta019, sta023, sta024, sta028, sta036, sta040, sta049, sta050, sta054, sta057, sta064, sta065, sta073, sta095, sta096, sta098, sta100, sta101, sta102, sta103, sta105, sta107, sta108, sta109, sta111, sta112, sta113, sta115, sta116, sta117, sta118, sta120, NW_06, NW_07, NW_08, NW_09, and NW_10, such as SEQ ID NO: 228 and 229, were identified as fragments of sta019.

偶联的荚膜糖可用于提供调理免疫力。血清型5和8覆盖约85％的临床分离物。Conjugated capsular saccharides can be used to provide opsonic immunity. Serotypes 5 and 8 cover approximately 85% of clinical isolates.

菌株覆盖度Strain coverage

利用一组36种临床分离物表示流行菌株，包括属于代表全球流行CA-MRSA(社区相关-甲氧西林耐药金黄色葡萄球菌)中绝大多数的5种同种细胞谱系的菌株。还包括HA-MRSA(医院相关MRSA)和非-MRSA菌株。该组总体上包括9种HA-MRSA菌株、7种CA-MRSA菌株、2种MRSA菌株和18种其它菌株。A panel of 36 clinical isolates was used to represent circulating strains, including strains belonging to 5 homologous cell lineages representing the vast majority of globally prevalent CA-MRSA (community-associated-methicillin-resistant Staphylococcus aureus). Also included are HA-MRSA (hospital associated MRSA) and non-MRSA strains. Overall, the panel included 9 HA-MRSA strains, 7 CA-MRSA strains, 2 MRSA strains and 18 other strains.

编码IsdA、Hla、EsxA、Sta006、Sta011、Spa和ClfB的基因存在于所有36种菌株中。36种菌株中有11种缺乏EsxB的基因，36种菌株中有6种缺乏SdrD的基因。Genes encoding IsdA, Hla, EsxA, Sta006, Sta011, Spa and CIfB were present in all 36 strains. Eleven of the 36 strains lacked the EsxB gene, and 6 of the 36 strains lacked the SdrD gene.

在该组中编码的IsdA序列有95-100％相同，该蛋白质在稳定生长期的铁限制条件下表达。在30/36SdrD+ve种组成员中编码的SdrD序列有95-100％相同。在该组中，编码的EsxA序列100％相同；在25种EsxB+ve菌株中编码的EsxB序列有95-100％相同。在该组中，编码的ClfB序列有93-100％相同，还发现在早期指数生长期该蛋白高度表面暴露。The IsdA sequence encoded in this group is 95-100% identical, and the protein is expressed under iron-limited conditions in the stationary growth phase. The encoded SdrD sequences were 95-100% identical among members of the 30/36SdrD +ve species group. In this group, the encoded EsxA sequences were 100% identical; the encoded EsxB sequences were 95-100% identical among the 25 EsxB +ve strains. In this group, the encoded CIfB sequence was 93-100% identical and the protein was also found to be highly surface exposed during early exponential growth phase.

编码的氨基酸序列中的保守性如下所示(％相同性)：Conservation in the encoded amino acid sequences is shown below (% identity):

  抗原 Antigen   IsdA IsdA   ClfB ClfB   SdrD SdrD   Spa spa   Hla Hla   EsxA EsxA   EsxB EsxB   Sta006 Sta006   ％ %   95-100 95-100   97-100 97-100   88-100 88-100   98-100 98-100   97-100 97-100   100 100   95-100 95-100   99.7-100 99.7-100

筛选61种菌株的较大组中是否存在编码Hla和Sta006的基因以及它们的表达。该组覆盖了各种地理来源和各种ST及同种复杂类型的MRSA和MSSA菌株。9/61种菌株不表达Hla，而除一种以外所有的菌株表达Sta006(第61种菌株的数据不确定)。因此，仅依据Hla的疫苗不可能得到通用疫苗的充足覆盖度，但可通过加入Sta006克服该问题。A larger panel of 61 strains was screened for the presence and expression of the genes encoding Hla and Sta006. The group covers MRSA and MSSA strains of various geographic origins and various ST and homogeneous complex types. 9/61 strains did not express Hla, while all but one strains expressed Sta006 (data inconclusive for the 61st strain). Therefore, it is impossible to obtain sufficient coverage of a universal vaccine with a vaccine based on Hla alone, but this problem can be overcome by adding Sta006.

细胞毒性和细胞结合研究Cytotoxicity and Cell Binding Studies

利用HBMEC和A549细胞进行金黄色葡萄球菌重组抗原Hla、Hla-H35L、IsdA、IsdB、sta006、sta011和EsxAB的潜在细胞毒性分析。采用膜联蛋白V和碘化丙锭染色通过流式细胞术检测早期和晚期凋亡细胞的百分比。内皮细胞在24孔板中生长至完全汇合。然后将细胞与3种不同浓度(10μg/ml、1μg/ml、0.1μg/ml)的重组抗原温育24小时。利用TNF-α和戊二酰亚胺环己酮(CHX)的组合作为阳性对照，据报道说该组合诱导内皮细胞凋亡。仅与PBS缓冲液温育是阴性对照。然后通过FACS进行分析。Potential cytotoxicity analysis of S. aureus recombinant antigens Hla, Hla-H35L, IsdA, IsdB, sta006, sta011 and EsxAB using HBMEC and A549 cells. The percentages of early and late apoptotic cells were detected by flow cytometry using annexin V and propidium iodide staining. Endothelial cells were grown to full confluence in 24-well plates. Cells were then incubated with recombinant antigen at 3 different concentrations (10 μg/ml, 1 μg/ml, 0.1 μg/ml) for 24 hours. A combination of TNF-[alpha] and cyclohexanone glutarimide (CHX), which was reported to induce apoptosis in endothelial cells, was used as a positive control. Incubation with PBS buffer only is a negative control. Analysis was then performed by FACS.

抗原无一对HBMEC或A549细胞诱导细胞毒性。实际上，与对照细胞相比，活细胞群体的百分数在最多达24小时的温育期间维持基本恒定。相反，TNF-α和CHX的组合诱导凋亡细胞数量增加25％。None of the antigens induced cytotoxicity against HBMEC or A549 cells. Indeed, the percentage of viable cell population remained essentially constant during up to 24 hours of incubation compared to control cells. In contrast, the combination of TNF-α and CHX induced a 25% increase in the number of apoptotic cells.

HBMEC也用作检验金黄色葡萄球菌重组抗原与人内皮细胞结合的体外模型。37℃，在加湿气氛中，利用补加了10％热灭活胎牛血清、10％NuSerum、2mM谷氨酰胺、1mM丙酮酸盐、1％非必需氨基酸、1％MEM维生素、100单位/毫升青霉素和100μg/ml链霉素的RPMI 1640培养基培养HBMEC至汇合。通过间接免疫荧光检验重组抗原与细胞的结合，通过FACS分析。结合阳性的细胞检测为相对于阴性对照(非特异性抗体识别)的净平均荧光强度。在4℃进行结合实验。各重组抗原的特异性小鼠多克隆抗体用作一抗，利用R-藻红蛋白-偶联的山羊抗-小鼠IgG二抗检测结合。作为阴性对照，HBMEC与用荧光标记二抗检测的第一多克隆抗体温育，或仅有荧光标记的二抗。已知的表面暴露GBS抗原的结合用作阳性对照。HBMEC was also used as an in vitro model to test the binding of S. aureus recombinant antigens to human endothelial cells. 37°C, in a humidified atmosphere, supplemented with 10% heat-inactivated fetal bovine serum, 10% NuSerum, 2mM glutamine, 1mM pyruvate, 1% non-essential amino acids, 1% MEM vitamins, 100 units/ml HBMECs were cultured in RPMI 1640 medium with penicillin and 100 μg/ml streptomycin to confluence. Binding of recombinant antigen to cells was examined by indirect immunofluorescence and analyzed by FACS. Binding-positive cells were detected as net mean fluorescence intensity relative to negative controls (non-specific antibody recognition). Binding experiments were performed at 4°C. Mouse polyclonal antibodies specific for each recombinant antigen were used as primary antibodies, and binding was detected with R-phycoerythrin-conjugated goat anti-mouse IgG secondary antibodies. As a negative control, HBMEC were incubated with primary polyclonal antibody detected with fluorescently labeled secondary antibody, or fluorescently labeled secondary antibody alone. Binding of known surface-exposed GBS antigens was used as a positive control.

Hla和Hla-H35L是能强效结合内皮细胞的唯一抗原。还检验了这两种抗原的溶血活性。Hla and Hla-H35L were the only antigens that strongly bound endothelial cells. The hemolytic activity of these two antigens was also examined.

利用去纤维蛋白的绵羊和家兔血液，通过分光光度法试验检测它们的溶血活性。37℃，将血液与两种蛋白质的1∶4连续稀释液温育30分钟。与水温育(导致渗透性溶解)和与金黄色葡萄球菌蛋白温育是阳性对照；血液与PBS+BSA 0.5％温育作为阴性对照。Using defibrinated sheep and rabbit blood, their hemolytic activity was tested by spectrophotometric assay. Blood was incubated for 30 minutes at 37°C with 1:4 serial dilutions of the two proteins. Incubation with water (resulting in osmotic lysis) and incubation with S. aureus protein were positive controls; incubation of blood with PBS+BSA 0.5% was a negative control.

重组天然Hla对家兔红细胞显示溶血活性，但其H35L突变体形式没有溶血活性。该突变体的溶血活性比野生型至少低150倍。两种蛋白质对绵羊血液均无溶血活性。Recombinant natural Hla shows hemolytic activity on rabbit erythrocytes, but its H35L mutant form has no hemolytic activity. The hemolytic activity of this mutant is at least 150 times lower than that of the wild type. Neither protein had hemolytic activity on sheep blood.

因此，候选金黄色葡萄球菌重组疫苗对A549上皮细胞系和HBMEC内皮细胞系不显示细胞毒性。重要的是，已知能在宿主细胞的质膜内形成孔的Hla(一种分泌型毒素)能结合A549细胞但不对它们诱导细胞毒性；其还能诱导家兔红细胞的溶血作用。相反，重组Hla-H35L是含有单氨基酸取代的变体毒素从而不能形成胞质裂解孔，其在人细胞系和家兔红细胞中均不诱导细胞破坏。这些发现表明Hla的这种突变体形式可更安全地用于疫苗组合物。其它抗原无一显示能结合宿主细胞。Therefore, the candidate S. aureus recombinant vaccine did not show cytotoxicity against the A549 epithelial cell line and the HBMEC endothelial cell line. Importantly, Hla, a secreted toxin known to form pores in the plasma membrane of host cells, binds to A549 cells without inducing cytotoxicity to them; it also induces hemolysis of rabbit erythrocytes. In contrast, recombinant Hla-H35L, a variant toxin containing a single amino acid substitution so as not to form a cytoplasmic lytic pore, did not induce cell destruction in both human cell lines and rabbit erythrocytes. These findings suggest that this mutant form of Hla may be used in vaccine compositions more safely. None of the other antigens were shown to bind host cells.

佐剂制剂Adjuvant preparation

用氢氧化铝配制所选的金黄色葡萄球菌蛋白候选抗原，单独配制或作为蛋白质的组合，含或不含荚膜多糖偶联物。优化制剂的pH和克分子渗透压浓度。Selected S. aureus protein candidate antigens were formulated with aluminum hydroxide, either alone or as a combination of proteins, with or without capsular polysaccharide conjugates. The pH and osmolality of the formulation are optimized.

抗原是EsxA-B、Sta006、Sta011、Hla-H35L、SdrD、IsdA、IsdA40-184、Sta019、Sta021、Sta073、ClfB45-552、SdrD53-592、SasF和IsdB。这些抗原配制成100μg/ml的单价抗原，或配制成各为50μg/ml的组合抗原。加入5μg/ml、10μg/ml或25μg/ml的5型或8型菌株的荚膜糖偶联物。利用10mM组氨酸缓冲液(pH 6.5)配制的2mg/ml氢氧化铝，含9mg/ml NaCl。Antigens were EsxA-B, Sta006, Sta011, Hla-H35L, SdrD, IsdA, IsdA40-184 , Sta019, Sta021, Sta073, CIfB45-552 , SdrD53-592 , SasF and IsdB. These antigens were formulated as monovalent antigens at 100 [mu]g/ml, or as combined antigens at 50 [mu]g/ml each. Capsular glycoconjugates of type 5 or type 8 strains were added at 5 μg/ml, 10 μg/ml or 25 μg/ml. 2 mg/ml aluminum hydroxide in 10 mM histidine buffer (pH 6.5), containing 9 mg/ml NaCl.

可以调整含或不含偶联物的所有单价和组合制剂至所需pH和克分子渗透压浓度。制剂的pH为6.2-7.3，克分子渗透压浓度为248-360mOsm/kg。制剂中排除甘油，因为其对克分子渗透压浓度有负面影响。All monovalent and combination formulations, with or without conjugates, can be adjusted to the desired pH and osmolarity. The pH of the preparation is 6.2-7.3, and the osmolality is 248-360 mOsm/kg. Glycerol was excluded from the formulation because of its negative impact on osmolality.

除了IsdA、IsdA40-184、Sta019和Sta073，各种单价和组合制剂中的所有测试蛋白质均良好吸附于氢氧化铝佐剂。With the exception of IsdA, IsdA 40-184 , Sta019 and Sta073, all tested proteins in various monovalent and combination formulations adsorbed well to aluminum hydroxide adjuvant.

各Sta006、Sta011、EsxA-B和Hla-H35L蛋白完全吸附，可使它们解吸而不改变它们的吸附前电泳分布。The individual Sta006, Sta011, EsxA-B and Hla-H35L proteins were completely adsorbed, allowing their desorption without altering their pre-adsorption electrophoretic profiles.

Sta006、Sta011、EsxA-B和Hla-H35L组合中的各抗原完全吸附，对于佐剂无抗原间竞争。除了IsdA40-184，Sta006、Sta011、EsxA-B和IsdA40-184组合中的各抗原也完全吸附，特性与单价蛋白相同。对于两种组合，可使抗原解吸而不改变它们的吸附前电泳分布。Each antigen in the combination of Sta006, Sta011, EsxA-B and Hla-H35L was completely adsorbed, and there was no competition between antigens for the adjuvant. In addition to IsdA 40-184 , each antigen in the combination of Sta006, Sta011, EsxA-B and IsdA 40-184 was also completely adsorbed with the same properties as the monovalent protein. For both combinations, the antigens can be desorbed without changing their pre-adsorption electrophoretic distribution.

额外存在的5型和/或8型偶联物也不改变抗原的吸附或解吸特征，例如与Sta006+Sta011+EsxA-B组合。The additional presence of type 5 and/or type 8 conjugates also does not alter the adsorption or desorption characteristics of the antigen, for example in combination with Sta006+Sta011+EsxA-B.

进行短稳定性研究(2周，4℃)以评估单价制剂的稳定性和抗原完整性。测试的所有制剂在它们的pH和克分子渗透压浓度下稳定。所有抗原维持完全吸附于佐剂。所有抗原保持它们的解吸特征。解吸后没有证据表明抗原的降解或凝聚增加。A short stability study (2 weeks, 4°C) was performed to assess the stability and antigenic integrity of the monovalent formulations. All formulations tested were stable at their pH and osmolality. All antigens remained fully adsorbed to the adjuvant. All antigens retained their desorption characteristics. There was no evidence of increased degradation or aggregation of the antigen after desorption.

效力检验efficacy test

检验各抗原sta006、sta011、sta012、sta017、sta019、sta021和sta028抵御1.2x107cfu的Newman菌株(5型)静脉内攻击的能力。结果示于图1。与对照相比，所有抗原降低细菌数，sta006、sta011和sta019的结果最佳。The ability of each antigen sta006, sta011, sta012, sta017, sta019, sta021 and sta028 to resist 1.2×10 7 cfu of Newman strain (type 5) intravenous challenge was tested. The results are shown in Figure 1. All antigens reduced the number of bacteria compared to the control, with the best results for sta006, sta011 and sta019.

测试了其它各抗原：(i)NW_10；(ii)IsdA40-184；(iii)Sta002；(iv)Sta003；(v)Sta073；(vi)Sta101；(vii)Sta014；(viii)Hla-PSGS；(ix)SdrDCnaB。与阴性对照组相比，攻击后15天的存活率增加为：(i)50％；(ii)19％；(iii)37％；(iv)43％；(v)25％；(vi)12％；(vii)25％；(viii)56％；(ix)39％。(ii) IsdA 40-184 ; (iii) Sta002; (iv) Sta003; (v) Sta073; (vi) Sta101; (vii) Sta014; (viii) Hla-PSGS ; (ix) SdrD CnaB . The increase in survival 15 days post-challenge compared to the negative control group was: (i) 50%; (ii) 19%; (iii) 37%; (iv) 43%; (v) 25%; (vi) 12%; (vii) 25%; (viii) 56%; (ix) 39%.

还检验了两种杂交多肽：(i)HlaH35L-EsxAB；(ii)Sta006-EsxAB。与阴性对照组相比，攻击后存活率的增加为(i)25％；(ii)25％。Two hybrid polypeptides were also tested: (i) HlaH35L-EsxAB; (ii) Sta006-EsxAB. The increase in survival after challenge was (i) 25%; (ii) 25% compared to the negative control group.

表2 总结了各种抗原在脓肿模型中得到的结果。Table 2 summarizes the results obtained for various antigens in the abscess model.

实验SA-10-a检验了抗原组合的效力。6组12只CD-1小鼠接受均添加氢氧化铝佐剂的阴性对照(PBS)、IsdB、或以下组合之一：(i)EsxAB+Hla-H35L；(ii)Sta006+Sta011+EsxAB；(iII)Sta006+Sta011+EsxAB+Hla-H35L；或(iv)Sta006+Sta011+IsdA40-184+EsxAB。在第0天和第14天进行两次给药。第24天时，小鼠接受3x108cfu Newman菌株葡萄球菌，每24小时评估各组中的存活率，共2周。结果示于图2。14天后，阳性对照组中25％的动物存活，但在组(ii)中50％的动物存活，组(iii)和(iv)中58％的动物存活，组(i)中75％存活。Experiment SA-10-a examined the potency of antigen combinations. 6 groups of 12 CD-1 mice received negative control (PBS), IsdB, or one of the following combinations all added with aluminum hydroxide adjuvant: (i) EsxAB+Hla-H35L; (ii) Sta006+Sta011+EsxAB; (iii) Sta006+Sta011+EsxAB+Hla-H35L; or (iv) Sta006+Sta011+IsdA 40-184 +EsxAB. Two doses were performed on day 0 and day 14. On day 24, mice received 3x108 cfu Newman strain Staphylococci and survival in each group was assessed every 24 hours for 2 weeks. The results are shown in Figure 2. After 14 days, 25% of the animals survived in the positive control group, but 50% of the animals survived in group (ii), 58% of the animals survived in groups (iii) and (iv), and 58% of the animals in group (i) survived. ) 75% survived.

实验SA-10-b采用相同的方法检验：(i)ClfB45-552+Hla-H35L+Sta006+EsxAB；(ii)ClfB45-552+Sta011+Sta006+EsxAB；(iii)ClfB45-552+IsdA40-184+Sta006+EsxAB；或(iv)SdrD53-592+IsdA40-184+Sta006+EsxAB。结果示于图3。14天后，阳性对照组和组(ii)中25％的动物存活，但在组(iv)中33％的动物存活，组(i)中75％的动物存活，组(iii)中83％的动物存活。Experiment SA-10-b was tested by the same method: (i) ClfB 45-552 + Hla-H35L + Sta006 + EsxAB; (ii) ClfB 45-552 + Sta011 + Sta006 + EsxAB; (iii) ClfB 45-552 + IsdA 40-184 +Sta006+EsxAB; or (iv) SdrD 53-592 +IsdA 40-184 +Sta006+EsxAB. The results are shown in Figure 3. After 14 days, 25% of the animals survived in the positive control group and group (ii), but 33% of the animals survived in the group (iv), 75% of the animals survived in the group (i), and the groups ( 83% of the animals in iii) survived.

还利用其它组合免疫小鼠。这些组合通常添加氢氧化铝佐剂(参见上文)，在第0和14天给予。在CD1小鼠中进行免疫，每组12只。在第24天，用致死剂量的活细菌攻击小鼠，然后再追踪14天的存活情况。为作比较，PBS用作阴性对照，IsdB作为阳性对照[2]。Mice were also immunized with other combinations. These combinations are usually adjuvanted with aluminum hydroxide (see above) and given on days 0 and 14. Immunization was carried out in CD1 mice, 12 in each group. On day 24, mice were challenged with a lethal dose of live bacteria and followed for an additional 14 days for survival. For comparison, PBS was used as a negative control and IsdB as a positive control [2].

实验SA-11检验：(i)5型偶联物与EsxAB+Sta006+Sta011的组合；(ii)EsxAB+Sta019+Sta006+Sta011；(iii)5型偶联物+Hla-H35L+Sta006+Sta011；(iv)EsxAB+Hla-H35L+Sta006+Sta011；或(v)EsxAB+IsdA40-184+Sta006+Sta011。攻击后14天，阴性对照动物均死亡，但42％的阳性对照动物存活。测试组中的存活结果如下所示：(i)67％；(ii)42％；(iii)75％；(iv)33％；和(v)25％。Experiment SA-11 test: (i) combination of type 5 conjugate and EsxAB+Sta006+Sta011; (ii) EsxAB+Sta019+Sta006+Sta011; (iii) type 5 conjugate+Hla-H35L+Sta006+Sta011 ; (iv) EsxAB+Hla-H35L+Sta006+Sta011; or (v) EsxAB+IsdA 40-184 +Sta006+Sta011. Fourteen days after challenge, all negative control animals died, but 42% of positive control animals survived. Survival results in the test groups were as follows: (i) 67%; (ii) 42%; (iii) 75%; (iv) 33%; and (v) 25%.

实验SA-12检验：(i)Hla-H35L+IsdA40-184+Sta006+Sta011；(ii)Hla-H35L+EsxAB+Sta006+Sta011；(iii)EsxAB+IsdA40-184+Sta006+Sta011；(iv)EsxAB+IsdA+Sta006+Sta011。攻击后14天，8％的阴性对照动物和17％的阳性对照动物存活。测试组中的存活结果如下所示：(i)50％；(ii)50％；(iii)25％；(iv)33％。Experiment SA-12 test: (i) Hla-H35L+IsdA 40-184 +Sta006+Sta011; (ii) Hla-H35L+EsxAB+Sta006+Sta011; (iii) EsxAB+IsdA 40-184 +Sta006+Sta011; ( iv) EsxAB+IsdA+Sta006+Sta011. 14 days after challenge, 8% of negative control animals and 17% of positive control animals survived. Survival results in the test groups were as follows: (i) 50%; (ii) 50%; (iii) 25%; (iv) 33%.

实验SA-14检验：(i)EsxAB+Hla-H35L+Sta006+Sta011；(ii)EsxAB+IsdA40-184+Sta006+Sta011；(iii)Sta006+Sta011+Sta019+EsxAB；(iv)Sta006+Sta011+Sta019+Hla-H35L。用5x108CFU Newman菌株攻击后14天，18％的阴性对照动物和9％的阳性对照动物存活；测试组中的存活结果如下所示：(i)58％；(ii)67％；(iii)42％；(iv)83％。14天的存活数量示于图4，显示在攻击后的每天，实施的所有组合优于两种对照。Experiment SA-14 test: (i) EsxAB+Hla-H35L+Sta006+Sta011; (ii) EsxAB+IsdA 40-184 +Sta006+Sta011; (iii) Sta006+Sta011+Sta019+EsxAB; (iv) Sta006+Sta011 +Sta019+Hla-H35L. 14 days after challenge with 5x10 8 CFU Newman strain, 18% of negative control animals and 9% of positive control animals survived; the survival results in the test groups are as follows: (i) 58%; (ii) 67%; (iii) ) 42%; (iv) 83%. The surviving numbers at 14 days are shown in Figure 4, showing that all combinations implemented outperformed both controls on each day post-challenge.

实验SA-17a检验：(i)EsxAB+Sta006+Sta011+血清型5偶联物+血清型8偶联物；(ii)EsxAB+Sta073+Sta011+血清型5偶联物+血清型8偶联物；(iii)EsxAB+Hla-H35L+Sta011+Sta073。与阴性对照相比，用Newman菌株攻击后15天的存活增加为(i)17％；(ii)42％；(iii)34％。组(ii)和(iii)的中值存活是完全的15天。组(i)中是12天。Experiment SA-17a test: (i) EsxAB+Sta006+Sta011+serotype 5 conjugates+serotype 8 conjugates; (ii) EsxAB+Sta073+Sta011+serotype 5 conjugates+serotype 8 conjugates; (iii) EsxAB+Hla-H35L+Sta011+Sta073. The increase in survival 15 days after challenge with the Newman strain was (i) 17%; (ii) 42%; (iii) 34% compared to the negative control. Median survival for groups (ii) and (iii) was 15 days complete. In group (i) it was 12 days.

其它抗原组合实验检验：(a)血清型5偶联物+血清型8偶联物+EsxAB+Sta006+Sta011；(b)Sta002+Sta003+Sta021+NW-10；(c)EsxAB+HlaH35L+Sta006+Sta019；和(d)EsxAB+Sta006+Sta019。与阴性对照相比，用Newman菌株攻击后的存活增加为(a)37％；(b)36％；(c)13％；和(d)0％。Other antigen combination experiments: (a) serotype 5 conjugate + serotype 8 conjugate + EsxAB + Sta006 + Sta011; (b) Sta002 + Sta003 + Sta021 + NW-10; (c) EsxAB + HlaH35L + Sta006 +Sta019; and (d) EsxAB+Sta006+Sta019. The increase in survival after challenge with the Newman strain was (a) 37%; (b) 36%; (c) 13%; and (d) 0% compared to the negative control.

合并研究SA-10、SA-11、SA-12和SA-14的存活数据以评估与PBS或IsdB相比的两种组合的效力。“Combo-1”是EsxAB+Hla-H35L+Sta006+Sta011(包含SEQ ID NO：241、150、246和247的多肽)。“Combo-2”是EsxAB+IsdA40-184+Sta006+Sta011。比较14天后，48只小鼠的各组的中值存活时间。PBS和IsdB组的中值存活时间为1天，“Combo-1”和“Combo-2”组中小鼠的中值存活时间为14天。通过t-检验比较中值存活持续时间的差异：“Combo-1”组中的存活在统计学上优于PBS组(p＜0.0001)和IsdB组(p＜0.0001)；“Combo-2”组中的存活在统计学上优于PBS组(p＜0.0001)和IsdB组(p＝0.0049)。这些数据示于图5。Survival data from studies SA-10, SA-11, SA-12 and SA-14 were pooled to assess the efficacy of the two combinations compared to PBS or IsdB. "Combo-1" is EsxAB+Hla-H35L+Sta006+Sta011 (comprising polypeptides of SEQ ID NO: 241, 150, 246 and 247). "Combo-2" is EsxAB+IsdA 40-184 +Sta006+Sta011. After 14 days, the median survival times of the groups of 48 mice were compared. The median survival time of the PBS and IsdB groups was 1 day, and the median survival time of the mice in the "Combo-1" and "Combo-2" groups was 14 days. Differences in median survival duration were compared by t-test: Survival in "Combo-1" group was statistically better than PBS group (p<0.0001) and IsdB group (p<0.0001);"Combo-2" group Survival in PBS group was statistically better than that of PBS group (p<0.0001) and IsdB group (p=0.0049). These data are shown in Figure 5.

图6显示Combo-1和Combo-2在脓肿模型中的数据。攻击后，分离小鼠的肾脏，然后匀浆并接种。cfu计数表明脓肿形成水平。图6显示一个实验的数据。数据以下的数值显示相比于PBS组的降低的对数。两个组合组中，降低大于单用IsdB，其中Combo-1的U-检验(单尾)值为0.0001，Combo-2的为0.0005。在第二实验的两个组合组中也观察到相同作用，其中不包括IsdB组。Figure 6 shows the data of Combo-1 and Combo-2 in the abscess model. After challenge, the kidneys of mice were isolated, then homogenized and inoculated. The cfu count indicates the level of abscess formation. Figure 6 shows data from one experiment. Values below the data show the log reduction compared to the PBS group. In the two combination groups, the reduction was greater than IsdB alone, where the U-test (one-tailed) value of Combo-1 was 0.0001 and that of Combo-2 was 0.0005. The same effect was also observed in the two combination groups of the second experiment, which did not include the IsdB group.

其它实验比较了Combo-1、IsdB或PBS获得的抵御以下3种不同菌株的保护作用：Staph-19、FPR3757(USA300)和Lac(USA300)。每组44只小鼠，结果如下所示(也参见图12)，包括存活部分的单尾p-值，其中：P1比较Combo-1与PBS；P2比较Combo-1与IsdB；P3比较PBS与IsdB：Other experiments compared the protection obtained by Combo-1, IsdB or PBS against 3 different strains: Staph-19, FPR3757 (USA300) and Lac (USA300). 44 mice per group, the results are shown below (see also Figure 12), including one-tailed p-values for the surviving fraction, where: P1 compares Combo-1 to PBS; P2 compares Combo-1 to IsdB; P3 compares PBS to IsdB:

Figure BPA00001481741801601
Figure BPA00001481741801601

其它实验显示与单用佐剂(氢氧化铝)或IsdB免疫相比，用Newman、USA100、CC30和USA300菌株攻击后添加佐剂的Combo1降低CFU计数。图10显示四种攻击菌株的CFU值(log/ml)。用Combo1获得最低的计数，各情况中p＜0.015。还评估了脓肿面积，Combo1-免疫小鼠中的也较低(例如，图11)。Additional experiments showed that adjuvanted Combo 1 reduced CFU counts after challenge with Newman, USA100, CC30 and USA300 strains compared to immunization with adjuvant (aluminum hydroxide) or IsdB alone. Figure 10 shows the CFU values (log/ml) of the four challenge strains. The lowest counts were obtained with Combo1, p<0.015 in each case. Abscess area was also assessed and was lower in Combol-immunized mice (eg, FIG. 11 ).

其它实验显示Combo1在败血症模型中对临床相关菌株提供高度保护作用，获得的存活％总是高于IsdB。图12显示用Newman、ST-80、FPR3757或Lac菌株攻击时，Combo1-免疫小鼠(每组40只，3次实验)的中值存活是完全的15天，存活小鼠的比例≥75％。相反，Newman和ST-80攻击后的IsdB-免疫小鼠的中值存活仅有1天，所有四种攻击菌株的存活＜65％。Other experiments have shown that Combo1 confers high protection against clinically relevant strains in a sepsis model, with %survival achieved always above IsdB. Figure 12 shows that when challenged with Newman, ST-80, FPR3757 or Lac strains, the median survival of Combo1-immunized mice (40 per group, 3 experiments) was a complete 15 days, and the proportion of surviving mice was ≥75% . In contrast, the median survival of IsdB-immunized mice following Newman and ST-80 challenge was only 1 day, with <65% survival for all four challenge strains.

比较Combo1与其单独的多肽Comparing Combo1 with its individual peptides

进行各种测试以比较Combo1与其4种单独的多肽(即，EsxAB、Hla-H35L、Sta006、Sta011)以及IsdB与无抗原阴性对照。Various tests were performed to compare Combol with its 4 individual polypeptides (ie, EsxAB, Hla-H35L, Sta006, Sta011) and IsdB with no antigen negative control.

检验免疫动物血清的调理吞噬活性。利用(i)单独的四种多肽，(ii)所述多肽的所有配对，(iii)所有三重组合或(iv)完整的Combo1组合得到血清。为作比较，利用抗-IsdB血清。该试验中，免疫前和阴性对照血清显示对Newman菌株无杀伤作用。在第一实验中：抗-IsdB血清显示27％的杀伤；抗4种单独多肽中每一种的血清显示26-34％的杀伤；所有的多种多肽组合显示至少34％的杀伤；Combo-1产生的血清显示39％的杀伤。在第二实验中：Combo-1显示43％的杀伤，但抗-IsdB血清杀伤略好；所有单一的或利用Combo-1多肽的多种多肽血清显示至少26％的杀伤。Test the opsonophagocytosis activity of immunized animal serum. Sera were obtained using (i) the four polypeptides alone, (ii) all pairs of said polypeptides, (iii) all triplet combinations or (iv) the complete Combo1 combination. For comparison, anti-IsdB serum was used. In this test, pre-immunization and negative control sera showed no killing effect on Newman strain. In the first experiment: Anti-IsdB serum showed 27% killing; Anti-4 individual polypeptides showed 26-34% killing; All multiple polypeptide combinations showed at least 34% killing; Combo- 1 The resulting serum showed 39% killing. In the second experiment: Combo-1 showed 43% killing, but anti-IsdB sera killed slightly better; all single or multiple polypeptide sera with Combo-1 polypeptide showed at least 26% killing.

其它实验观察到通过将免疫家兔的抗血清递送给小鼠(每组20只，8周龄CD1小鼠)实现的被动保护作用。4组接受用EsxAB、Hla-H35L、Sta006和Sta011之一免疫的家兔的200μl血清；第5组接受50μl各血清(共200μl)。其它两组接受IsdB-免疫家兔的血清或盐水+佐剂免疫家兔的血清。15分钟后，腹膜内攻击小鼠(108CFU Newman菌株)，14天后评估死亡率。结果如下所示：Other experiments observed passive protection by delivering antisera from immunized rabbits to mice (20 per group, 8-week-old CD1 mice). Group 4 received 200 μl of serum from rabbits immunized with one of EsxAB, Hla-H35L, Sta006 and Sta011; Group 5 received 50 μl of each serum (200 μl in total). The other two groups received sera from IsdB-immunized rabbits or saline+adjuvant immunized rabbits. Fifteen minutes later, mice ( 108 CFU Newman strain) were challenged intraperitoneally and mortality was assessed 14 days later. The result looks like this:

  EsxA-B EsxA-B   Sta006 Sta006   Sta011 Sta011   HlaH35L HlaH35L   Combo1 Combo1   IsdB IsdB   -ve对照 -ve control   存活 Survive   5％ 5%   26％ 26%   0％ 0%   15％ 15%   25％ 25%   10％ 10%   5％ 5%

在其它实验中，检测CD1小鼠中诱导的特异性抗体水平以评估Combo1中4种多肽的免疫原性。组合物包括各20μg的四种单独多肽，或4x10μg的组合。组合物包含氢氧化铝佐剂。通过Luminex 4Plex试验测定抗原特异性IgG的血清水平。如图9所示，所有4种多肽的本身或组合在CD1小鼠中显示高度免疫原性。在各情况中，组合给予时抗某多肽的滴度高于单独给予时(比较居中和右侧的配对)。In other experiments, the level of specific antibodies induced in CD1 mice was detected to evaluate the immunogenicity of the 4 polypeptides in Combo1. Compositions included 20 μg each of the four individual polypeptides, or 4x10 μg in combination. The composition includes an aluminum hydroxide adjuvant. Serum levels of antigen-specific IgG were determined by the Luminex 4Plex assay. As shown in Figure 9, all four polypeptides were highly immunogenic in CD1 mice by themselves or in combination. In each case, titers against a polypeptide were higher when administered in combination than when administered alone (compare center and right pairings).

其它实验比较Combo-1或其4种单独多肽实现的保护作用。也包括IsdB以供比较。Newman菌株攻击后15天的存活动物比例(每组40只动物)，和各天的平均(中值)存活如下所示，包括与PBS+佐剂阴性对照相比较的存活部分的单尾p-值：Other experiments compared the protection achieved by Combo-1 or its four individual polypeptides. IsdB is also included for comparison. The proportion of animals surviving 15 days after Newman strain challenge (40 animals per group), and the mean (median) survival for each day are shown below, including one-tailed p-values for the surviving fraction compared to the PBS+adjuvant negative control :

  EsxA-B EsxA-B   Sta006 Sta006   Sta011 Sta011   HlaH35L HlaH35L   Combo1 Combo1   IsdB IsdB   PBS PBS   存活 Survive   34％ 34%   28％ 28%   16％ 16%   39％ 39%   59％ 59%   22％ twenty two%   5％ 5%   P P   0.0017 0.0017   0.0003 0.0003   0.0064 0.0064   ＜0.0001 ＜0.0001   ＜0.0001 ＜0.0001   0.0006 0.0006   - -   天 sky   1 1   2 2   1 1   10 10   15 15   1 1   0 0

利用小鼠脓肿模型比较4种单独的多肽与Combo1组合。在一些实验中，用IsdB免疫小鼠以供比较。给抗原添加氢氧化铝作为佐剂，单独的佐剂用作阴性对照。图7显示4种不同菌株攻击后动物肾脏中的细菌数。观察到Combo1组合的平均计数最低。Comparison of 4 individual peptides in combination with Combo1 using a mouse abscess model. In some experiments, mice were immunized with IsdB for comparison. Aluminum hydroxide was added to the antigen as an adjuvant and the adjuvant alone was used as a negative control. Figure 7 shows the number of bacteria in the kidneys of animals after challenge with 4 different strains. The Combo1 combination was observed to have the lowest mean count.

用(i)单独的四种多肽，(ii)所有配对，(iii)所有三重组合或(iv)完整的Combo1组合免疫后进行攻击实验。单用IsdB或缓冲液进行比较。用5x108CFU Newman菌株攻击后，每组24只小鼠的存活(3次实验)示于图13。IsdB的中值存活只有2天。各Combo1多肽的中值存活为1-6天。多肽配对获得的中值存活为2-11天。三重组合获得的中值存活为8-15天。完全的Combo1组合得到的中值存活为完整的15天，59％的小鼠活了如此长的时间(相比之下，利用IsdB仅为35％)。Challenge experiments were performed after immunization with (i) the four polypeptides alone, (ii) all pairs, (iii) all triplet combinations, or (iv) the complete Combo1 combination. Comparisons were made with IsdB alone or buffer. The survival of 24 mice per group (3 experiments) after challenge with 5x10 8 CFU of Newman strain is shown in FIG. 13 . The median survival for IsdB was only 2 days. The median survival for each Combol polypeptide was 1-6 days. The median survival obtained for polypeptide pairings was 2-11 days. The median survival obtained with the triple combination was 8-15 days. The full Combo1 combination gave a median survival of a full 15 days, 59% of mice surviving this long (compared to only 35% with IsdB).

应该知道，仅仅通过例子描述了本发明，可作出改进而仍维持在本发明的范围和构思内。It should be understood that the invention has been described by way of example only and that modifications may be made while remaining within the scope and spirit of the invention.

表1：命名交叉参考Table 1: Named cross-references

Figure BPA00001481741801621
Figure BPA00001481741801621

Figure BPA00001481741801631
Figure BPA00001481741801631

Figure BPA00001481741801641
Figure BPA00001481741801641

Figure BPA00001481741801651
Figure BPA00001481741801651

表2：脓肿模型结果总结Table 2: Summary of Abscess Model Results

Figure BPA00001481741801652
Figure BPA00001481741801652

Figure BPA00001481741801661
Figure BPA00001481741801661

Figure BPA00001481741801671
Figure BPA00001481741801671

Figure BPA00001481741801681
Figure BPA00001481741801681

*明矾＝氢氧化铝 * Alum = aluminum hydroxide

**肾脏CFU降低的对数 ** Log reduction in renal CFU

参考文献references

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[2]Kuklin等.(2006)Infect Immun.74(4)：2215-23.[2] Kuklin et al. (2006) Infect Immun.74(4): 2215-23.

[3]WO2007/113222.[3]WO2007/113222.

[4]WO2005/009379.[4]WO2005/009379.

[5]WO2009/029132.[5]WO2009/029132.

[6]WO2008/079315.[6]WO2008/079315.

[7]WO2005/086663.[7]WO2005/086663.

[8]WO2005/115113.[8]WO2005/115113.

[9]WO2006/033918.[9]WO2006/033918.

[10]WO2006/078680.[10]WO2006/078680.

[11]WO2007/113224.[11]WO2007/113224.

[12]WO98/10788.[12]WO98/10788.

[13]WO2007/053176.[13]WO2007/053176.

[14]O’Brien等.(2000)J Dairy Sci 83：1758-66.[14] O'Brien et al. (2000) J Dairy Sci 83: 1758-66.

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Claims (20)

1. immunogenic composition, it comprises antigenic combination, and said combination comprises two kinds or the more kinds of antigen that is selected from down group: (1) sta006 antigen; (2) sta011 antigen; (3) esxA antigen; (4) esxB antigen; (5) hla antigen; (6) ebpS antigen; (7) efb antigen; (8) emp antigen; (9) esaC antigen; (10) coA antigen; (11) eap antigen; (12) FnBA antigen; (13) FnBB antigen; (14) ebhA antigen; (15) hlgB antigen; (16) hlgC antigen; (17) isdA antigen; (18) isdB antigen; (19) isdC antigen; (20) isdG antigen; (21) isdH antigen; (22) isdI antigen; (23) lukD antigen; (24) lukE antigen; (25) lukF antigen; (26) lukS antigen; (27) nuc antigen; (28) sasA antigen; (29) sasB antigen; (30) sasC antigen; (31) sasD antigen; (32) sasF antigen; (33) sdrC antigen; (34) sdrD antigen; (35) sdrE2 antigen; (36) spa antigen; (37) clfA antigen; (38) clfB antigen; (39) sta001 antigen; (40) sta002 antigen; (41) sta003 antigen; (42) sta004 antigen; (43) sta005 antigen; (44) sta007 antigen; (45) sta008 antigen; (46) sta009 antigen; (47) sta010 antigen; (48) sta012 antigen; (49) sta013 antigen; (50) sta014 antigen; (51) sta015 antigen; (52) sta016 antigen; (53) sta017 antigen; (54) sta018 antigen; (55) sta019 antigen; (56) sta020 antigen; (57) sta021 antigen; (58) sta022 antigen; (59) sta023 antigen; (60) sta024 antigen; (61) sta025 antigen; (62) sta026 antigen; (63) sta027 antigen; (64) sta028 antigen; (65) sta029 antigen; (66) sta030 antigen; (67) sta031 antigen; (68) sta032 antigen; (69) sta033 antigen; (70) sta034 antigen; (71) sta035 antigen; (72) sta036 antigen; (73) sta037 antigen; (74) sta038 antigen; (75) sta039 antigen; (76) sta040 antigen; (77) sta041 antigen; (78) sta042 antigen; (79) sta043 antigen; (80) sta044 antigen; (81) sta045 antigen; (82) sta046 antigen; (83) sta047 antigen; (84) sta048 antigen; (85) sta049 antigen; (86) sta050 antigen; (87) sta051 antigen; (88) sta052 antigen; (89) sta053 antigen; (90) sta054 antigen; (91) sta055 antigen; (92) sta056 antigen; (93) sta057 antigen; (94) sta058 antigen; (95) sta059 antigen; (96) sta060 antigen; (97) sta061 antigen; (98) sta062 antigen; (99) sta063 antigen; (100) sta064 antigen; (101) sta065 antigen; (102) sta066 antigen; (103) sta067 antigen; (104) sta068 antigen; (105) sta069 antigen; (106) sta070 antigen; (107) sta071 antigen; (108) sta072 antigen; (109) sta073 antigen; (110) sta074 antigen; (111) sta075 antigen; (112) sta076 antigen; (113) sta077 antigen; (114) sta078 antigen; (115) sta079 antigen; (116) sta080 antigen; (117) sta082 antigen; (118) sta083 antigen; (119) sta084 antigen; (120) sta085 antigen; (121) sta086 antigen; (122) sta087 antigen; (123) sta088 antigen; (124) sta089 antigen; (125) sta090 antigen; (126) sta091 antigen; (127) sta092 antigen; (128) sta093 antigen; (129) sta094 antigen; (130) sta095 antigen; (131) sta096 antigen; (132) sta097 antigen; (133) sta098 antigen; (134) sta099 antigen; (135) sta100 antigen; (136) sta101 antigen; (137) sta102 antigen; (138) sta103 antigen; (139) sta104 antigen; (140) sta105 antigen; (141) sta106 antigen; (142) sta107 antigen; (143) sta108 antigen; (144) sta109 antigen; (145) sta110 antigen; (146) sta111 antigen; (147) sta112 antigen; (148) sta113 antigen; (149) sta114 antigen; (150) sta115 antigen; (151) sta116 antigen; (152) sta117 antigen; (153) sta118 antigen; (154) sta119 antigen; (155) sta120 antigen; (156) NW_6 antigen; (157) NW_9 antigen; (158) NW_10 antigen; (159) NW_7 antigen; (160) NW_8 antigen; (161) NW_2 antigen; (162) NW_1 antigen; (163) sta081 antigen; (164) NW_5 antigen.
2. compositions as claimed in claim 1 is characterized in that, said compositions comprises at least a antigen that is selected from (3) to (38) and at least a antigen that is selected from (1), (2) and (37) to (149).
3. compositions as claimed in claim 2 is characterized in that, said compositions comprises:
Be selected from least a antigen of (37), (38), (8), (9), (3), (4), (5), (17), (18), (19), (31), (32), (33), (34), (35) or (36);
With at least a antigen that is selected from (40), (1), (43), (2), (64), (96), (133) or (147).
4. compositions as claimed in claim 1 is characterized in that, said compositions comprises two kinds or the more kinds of antigen that is selected from down group: (1) clfA antigen; (2) clfB antigen; (3) sdrE2 antigen; (4) sdrC antigen; (5) SasF antigen; (6) emp antigen; (7) sdrD antigen; (8) spa antigen; (9) esaC antigen; (10) esxA antigen; (11) esxB antigen; (12) sta006 antigen; (13) isdC antigen; (14) hla antigen; (15) sta011 antigen; (16) isdA antigen; (17) isdB antigen; (18) sasF antigen.
5. compositions as claimed in claim 1 is characterized in that, said compositions comprises two kinds or the more kinds of antigen that is selected from down group: (1) esxA antigen; (2) esxB antigen; (3) sta006 antigen; (4) hla antigen; (5) sta011 antigen.
6. according to any one of the preceding claims compositions is characterized in that one or more said antigens are adsorbed in aluminum hydroxide adjuvant, and optional wherein said compositions comprises histidine buffer.
7. according to any one of the preceding claims compositions is characterized in that said compositions also comprises: (i) staphylococcus aureus (S.aureus) exopolysaccharide and (ii) one or more conjugates of carrier protein.
8. according to any one of the preceding claims compositions is characterized in that said compositions also comprises: (i) staphylococcus aureus capsular polysaccharide and (ii) one or more conjugates of carrier protein.
9. formula NH 2-A-{-X-L-} nPolypeptide shown in the-B-COOH, wherein:
X is the antigenic aminoacid sequence of staphylococcus, is selected from down group: staphylococcus aureus antigen sta006, sta011, esxA, esxB, hla, clfA, clfB, coA, eap, ebhA, ebpS, efb, emp, esaC, FnBA, FnBB, hlgB, hlgC, isdA, isdB, isdC, isdG, isdH, isdI, lukD, lukE, lukF, lukS, nuc, sasA, sasB, sasC, sasD, sasF, sdrC, sdrD, sdrE2, spa, sta001, sta002, sta003, sta004, sta005, sta007, sta008, sta009, sta010, sta012, sta013, sta014, sta015, sta016, sta017, sta018, sta019, sta020, sta021, sta022, sta023, sta024, sta025, sta026, sta027, sta028, sta029, sta030, sta031, sta032, sta033, sta034, sta035, sta036, sta037, sta038, sta039, sta040, sta041, sta042, sta043, sta044, sta045, sta046, sta047, sta048, sta049, sta050, sta051, sta052, sta053, sta054, sta055, sta056, sta057, sta058, sta059, sta060, sta061, sta062, sta063, sta064, sta065, sta066, sta067, sta068, sta069, sta070, sta071, sta072, sta073, sta074, sta075, sta076, sta077, sta078, sta079, sta080, sta081, sta082, sta083, sta084, sta085, sta086, sta087, sta088, sta089, sta090, sta091, sta092, sta093, sta094, sta095, sta096, sta097, sta098, sta099, sta100, sta101, sta102, sta103, sta104, sta105, sta106, sta107, sta108, sta109, sta110, sta111, sta112, sta113, sta114, sta115, sta116, sta117, sta118, NW_6, NW_9, NW_10, NW_7, NW_8, NW_2, NW_1 and NW_5;
L is the joint aminoacid sequence of choosing wantonly;
A is the-terminal amino acid sequence of choosing wantonly;
B is the C-terminal amino acid sequence of choosing wantonly; With
N is 2 or higher integer.
10. immunogenic composition that comprises the said polypeptide of claim 9, said compositions also comprises: (A) (i) staphylococcus aureus exopolysaccharide and (ii) one or more conjugates of carrier protein; And/or (B) (i) staphylococcus aureus capsular polysaccharide and (ii) one or more conjugates of carrier protein.
11. compositions according to any one of the preceding claims or polypeptide is characterized in that, said clfA antigen can cause the antibody of identification SEQ ID NO:1 and comprise following aminoacid sequence: (a) have 80% or higher homogeny with SEQID NO:1; And/or (b) comprising the fragment of at least 7 contiguous amino acids of SEQ ID NO:1, wherein said fragment comprises the epi-position from SEQ ID NO:1.
12. polypeptide that comprises following aminoacid sequence: (a) have 80% or higher homogeny with SEQ ID NO:151; And/or (b) comprising the fragment of at least 7 contiguous amino acids of amino acid/11 04-207 of at least 7 contiguous amino acids and SEQ ID NO:151 of the amino acid/11-97 of SEQ ID NO:151, wherein said polypeptide can cause the wild type protein staphylococcus and the antibody that comprises the wild type protein staphylococcus of SEQ ID NO:11 that identification comprises SEQ ID NO:10.
13. an immunogenic composition, said compositions comprise described polypeptide of claim 12 and (i) sta006 antigen; (ii) hla antigen; And/or (iii) one or more in the sta011 antigen.
14. compositions as claimed in claim 13 is characterized in that, said compositions comprises adjuvant.
15. a peptide species, the aminoacid sequence that said polypeptide comprises be selected from down the aminoacid sequence of organizing and have 80% or higher homogeny: SEQ ID NO:151,152,168,202,203,204,205,206,207,208,209,210,211,212,220,221,222,223,224,237,238,241.
16. a peptide species, said polypeptide comprise the aminoacid sequence that is selected from down group: SEQ ID NO:151,152,168,202,203,204,205,206,207,208,209,210,211,212,220,221,222,223,224,237,238,241,242,243,244,245.
17. a peptide species, said polypeptide comprises: (a) have 90% or first sequence of higher homogeny with SEQ ID NO:218; (b) have 90% or second sequence of higher homogeny with SEQ ID NO:219, wherein said first and second sequences directly connect or connect through being less than 10 amino acid whose aminoacid sequences that interleave.
18. a pharmaceutical composition, said compositions comprise each described polypeptide in the claim 12,15,16 or 17.
19. a method that in mammal, produces immunne response, said method comprise the step of each said polypeptide in the above claim that gives said mammal effective dose or compositions.
20. the nucleic acid of coding claim 9,12,15,16 or 17 said polypeptide.
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CN102993308A (en) * 2012-09-29 2013-03-27 重庆原伦生物科技有限公司 Methicillin-resistant staphylococcus aureus (MRSA) vaccine recombinant protein antigen HI2 and preparation method and application thereof
CN104619336A (en) * 2012-08-31 2015-05-13 诺华股份有限公司 Stabilized proteins for immunity against Staphylococcus aureus
CN104684570A (en) * 2012-08-31 2015-06-03 诺华股份有限公司 Stabilised proteins for immunising against staphylococcus aureus
CN104736165A (en) * 2012-08-31 2015-06-24 诺华股份有限公司 Stabilised proteins for immunising against Staphylococcus aureus
CN107224576A (en) * 2017-03-06 2017-10-03 浙江海隆生物科技有限公司 Vaccine of staphylococcus aureus mastitis in dairy cows subunit and its preparation method and application
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